Archive for the ‘Medicinal Chemistry’ Category

Optimer Pharmaceuticals Receives Milestone Payment From Cempra for Next-Generation Macrolide Antibiotic

Last Updated on Saturday, 24 July 2010 04:26 Written by admin Thursday, 8 July 2010 11:02

SAN DIEGO, July 8 /PRNewswire-FirstCall/ – Optimer Pharmaceuticals, Inc. today announced it has received a $500,000 milestone payment from Cempra Pharmaceuticals, Inc. pursuant to the terms of a licensing agreement between the companies. Â The milestone payment was made as a result of Cempra’s continuing development of a next-generation macrolide (CEM-101) for the treatment of respiratory infections. Cempra licensed CEM-101 from Optimer and has successfully completed a Phase 1 study.

“The successful completion of the CEM-101 Phase 1 study further validates our OPopSâ„¢ drug discovery platform. We are pleased to see this compound progress into the next phase of development by Cempra,” said Pedro Lichtinger, Optimer’s President and CEO.

CEM-101 is a next-generation oral macrolide entering Phase 2 clinical development for the treatment of community-acquired bacterial pneumonia (CABP). Cempra has exclusive worldwide rights, except in Association of Southeast Asian Nations, or ASEAN, countries, from Optimer to discover, develop and commercialize macrolides from a library of more than 500 compounds, including CEM-101, originated from Optimer’s OPopS drug discovery platform.

In vitro and in vivo studies of CEM-101 have shown potent activity against S. pneumoniae as well as an extended spectrum of activity against community-associated methicillin-resistant Staphylococcus aureaus (CA-MRSA), M. avium and in animal models of malaria. These studies have also indicated that CEM-101 is active against atypical bacteria, such as Legionella, Mycoplasma and Ureaplasma and against gonococci and other organisms that cause genitourinary tract infections.

About OPopSâ„¢

Optimer’s OPopS drug discovery platform allows the development of potential drug candidates through carbohydrate mediated medicinal chemistry and enables the rapid synthesis of a wide variety of proprietary molecules. It includes GlycoOptimization, which enables the modification of a carbohydrate group on an existing drug to improve its properties, and De Novo Glycosylation, which introduces new carbohydrate groups on existing drugs to create new patentable compounds with improvement of pharmacokinetics.

About Optimer Pharmaceuticals

Optimer Pharmaceuticals, Inc. is a biopharmaceutical company focused on discovering, developing and commercializing innovative anti-infectives to treat serious infections and address unmet medical needs. Optimer has two late-stage anti-infective product candidates under development. Fidaxomicin is a narrow spectrum antibiotic being developed for the treatment of Clostridium difficile infection (CDI). Â In two Phase 3 trials completed by Optimer to study the safety and efficacy of fidaxomicin for the treatment of CDI, fidaxomicin was statistically superior to vancomycin in global cure rate (defined as cure with no recurrence within four weeks of completing therapy)Â as well as statistically superior in reducing recurrences of CDI by up to 50% when compared with vancomycin, the only FDA approved product for CDI. Pruvelâ„¢ is a prodrug in the fluoroquinolone class of antibiotics being developed as a treatment for infectious diarrhea.Â Optimer has also successfully completed two Phase 3 trials with Pruvel.Â Additional information can be found at http://www.optimerpharma.com.

Posted under BioInformatics, Business and Investment, Drug Development, Medicinal Chemistry, North America, Press Releases | No Comments

Sanford-Burnham robots speed up path to discovery

Last Updated on Saturday, 24 July 2010 04:26 Written by admin Thursday, 8 July 2010 10:40

The work force at Lake Nona’s Sanford- Burnham Institute includes 90 scientific staffers, 60 administrators and support personnel â€” and a team of three robots. The robots are part of a $15 million investment from the National Institutes of Health and occupy a large, glass-enclosed room on the bottom floor of Burnham’s Lake Nona campus.

Although they resemble the robotic arms used in automobile assembly lines, these robots have a far different task: filling test tubes faster than a human being. And that, scientists say, will speed up the process of scientific discovery.

“The robots are from the automobile industry,” said Greg Roth, director of medicinal chemistry at Burnham’s Conrad Prebys Center for Chemical Genomics. “We use them because of the accuracy and precision of their movements.”

The robotic arms can fill miniature test-tube “wells” so tiny that 1,536 of them fit on a plate the size of an index card. Using such small test tubes allows researchers to save money on chemicals and compounds.

After filling the wells, the robotic arms take a plate of the tubes and subject them to numerous tests such as varying temperatures and pressures. The robots are connected to a main computer that compiles the data from the millions of tests.

Pharmaceutical companies developed the ultra-high throughput screening technology in the mid-1990s, but universities and nonprofit research institutions such as Burnham did not have access to the robots until recently.

Funded by NIH, the Burnham center and eight others around the country form the institute’s Molecular Libraries Production Centers Network. This resource library and network assists scientists in research and allows results to be shared across the public and private sectors.

The reason for the federal government’s interest? As the results of the Human Genome Project began pouring in, scientists found themselves with so many avenues to explore that they needed faster research procedures.

“My scientists like to say they can do more than a robot, but they can only do it for a day,” said Michelle Palmer, director of screening for the Broad Institute at Harvard and Massachusetts Institute of Technology.

“The humans can do it faster and better, but they can’t sustain it. We need to sustain this over months of effort and get it done exactly the same way every time,” Palmer said.

Posted under Business and Investment, Education, Equipment & Supplies, HT Screening, Medicinal Chemistry, North America, Press Releases | No Comments

TimTec’s Contract Research Services

Last Updated on Thursday, 8 July 2010 10:18 Written by Editor Thursday, 8 July 2010 03:22

High Quality Organic Synthesis and Medicinal Chemistry Contract Research Services at an Outstanding Value

TimTec brings 15 years of expertise in organic chemistry design and supply for drug discovery closer to your supplemental bench-top requirements by launching The Organic Synthesis and Medicinal Chemistry Contract Research Services Division. TimTec scientists have a proven track record of providing high quality services and showing outstanding integrity to their clients.

TimTec remains flexible in delivering practical chemistry solutions molded to custom research requirements and budgets. All Contract Research Services are delivered with an emphasis on speed, real-time feedback, ongoing communication, superior compound quality, and the protection of our clientsâ€™ knowledge resources and interests. We are dedicated to providing these services at exceptionally competitive prices.

The Head of Contract Research Services has over 20 years of research experience in the US pharmaceutical industry as a hands-on medicinal chemistÂ and project Team Leader at large companies and smaller, start-up operations. We are keenly aware of all the intricate details and chemistry challenges that go into bench-top research before a qualified lead molecule emerges. Your TimTec contract research team consists of experienced, bench level scientists who have access to state of the art synthesis, analytical and quality control facilities.

TimTec Contract Research Services Start with:

Flexible Contracts
Program Management
State of the Art Facilities
Structure-Activity Relationship Evaluation
Lead Optimization
Property Optimization for ADME and PK
Metabolite Synthesis
Enabling Technologies â€“ Parallel synthesis, multistep synthesis, analytical chemistry
Mg to Kg Capacity
Compound Distribution â€“ Solid or solution, vials or plates
Patent Application Preparation Assistance

Supplemental Services and Products:

Custom Synthesis
Compound Acquisition
Weighting and Plating
HTS compounds and compound collections â€“ ActiMol Line of products

Posted under ADMET Studies, Drug-Like Compounds, Medicinal Chemistry, New Products, North America, R & D, Research Projects | No Comments

Potent Novel Tool For Combating Autoimmune Diseases And Leukemia

Last Updated on Thursday, 28 January 2010 06:10 Written by Editor Thursday, 28 January 2010 06:10

A study carried out by the scientists at the Scripps Research Institute illustrated a novel, highly practical strategy for identifying molecules that avert a particular form of immune cells from launching assaults on their host. These findings have added a potent new-fangled tool to the ongoing investigation for probable treatments for autoimmune diseases like MS or multiple sclerosis

, as well as for the treatment of types of leukemia like myeloid leukemia.

The study conducted by Thomas Kodadek, a professor in the Chemistry and Cancer Biology Departments, Scripps Florida, and associates was printed in the â€˜Chemistry & Biologyâ€™ Journal.

In the novel study, Kodadek and his associates utilised samples taken from an animal model of MS for screening for T cells â€“ a kind of white blood cell that dons fundamental role in the immune system â€“ with an increasing presence in the ailment. The screen additionally recognized molecules that interfered with such T cellsâ€™ auto-reactive nature or their assault on the body itself instead of a foreign intruder like a virus or bacteria.

Autoreactive t cells Kodadek stated that their method concurrently unearths and separates auto-reactive T cells along with inhibitors to them. A dual achievement at the core of which is a relative screening procedure of healthy T cells vs. Disease-causative T cells. Even as the process is technically complex and intricate, the thought behind it is not. The scientists intended to make the process of recognizing compounds simpler that could hinder auto-reactive T cells with outstanding specificity and the scientists were able to accomplish their objective.

The scientists employed a model of MS â€“ an autoimmune inflammatory condition that affects the brain and the spinal cord for the study. MS is a condition wherein the immune system assaults the myelin sheath coating and defensive nerve cells that lead to a host of symptoms dependent on what component of the nervous system has been affected. Prevalent signs of the condition involve weariness, numbing sensation; difficulties experienced in walking balancing and co-ordination; dysfunctional bladder and bowel; ocular problems; giddiness and vertigo; sexual dysfunction problems; pain, mental problems; emotional variations and spastic behaviours.

Simplification of the Process

Kodadek and his associates set up the novel method for shedding light on these autoimmune diseases and other kinds of disorders and produced a vast assortment of peptoids â€“molecules linked to, though more constant as compared to the peptides which made up the proteins. By organizing thousands of the peptides microscopically, the prototype of binding antibodies (a form of autoimmune molecule) and peptoids could be pictured. By observing samples drawn from animal models of an identified disease such as MS, peptoids which exhibited binding to antibodies closely linked with that disease could be easily identified.

Even better, peptoids which showed binding to the autoreactive T cells could be spotted with no awareness of the particular antigen (molecules that elicit the immune assault), offering an impartial approach with which to explore potentially beneficial compounds.

Kodadek stated that they had made a breakthrough where they set up a system that identifies T cell receptors which are copious in an ailing animal and in sapped levels in a healthy animal.

Potential for Curative Breakthrough

The novel process created a novel potential for curative finding. Molecules that targeted auto-reactive T cells in a direct way, while overlooking those T cells that identify foreign antigens, could provide the basis for a new drug development program intended at elimination of autoreactive cells with no affect on the normal functioning of the immune system.

Kodadek stated that the novel study is not the ultimate solution as it employed a model of MS elicited by a sole antigen whereas in human beings there could be 2 to even more antigens that trigger an autoimmune disease like MS that needs further investigation. The method could be applicable with ease to blood cancers, although as the disease-causative T cells have been completely characterized and there being quite a few of them.

Source: simplehealthguide.com

Posted under Medicinal Chemistry, Press Releases, R & D | No Comments

3rd International Symposium on Advances in Synthetic and Medicinal Chemistry

Last Updated on Sunday, 10 May 2009 10:19 Written by admin Sunday, 10 May 2009 10:19

Kiev, Ukraine, August 23 – 27, 2009

ASMC09 in Kiev is being prepared by EFMC (European Federation for Medicinal Chemistry) and ChemBridge Corporation, in the series of events which started with ASCMC04 Moscow followed by ASMC07 St. Petersburg.

Prof. Erick Carreira, ETH Zurich, Switzerland and Dr Scott Biller, Novartis Institutes for BioMedical Research, Cambridge, USA, have kindly accepted to be the Chairmen of the Symposium.

The scientific program of the International Symposium on Advances in Synthetic and Medicinal Chemistry will include:

* 28 invited plenary lectures, presented by highly recognized scientists from academia and the pharmaceutical and biotech industry from Europe, USA and former USSR countries.
* 10 short oral communications which will be selected from submitted abstracts
* poster sessions

The scientific program will be complemented by an attractive cultural program in Kiev.

The topics to be covered during this symposium include:

* New Synthetic Methodologies, Total Synthesis of Natural Products and Heterocyclic Chemistry
* Diversity- and Target-Oriented Synthesis and Chemical Biology
* Medicinal Chemistry and Drug Discovery & Development

The program will also include a commercial exhibition and a half-day Business Mini-Symposium â€œSmall Molecule Screening Libraries in Drug Discovery: Experience and Trendsâ€.

The official language of the symposium is English.

http://www.ldorganisation.com

Posted under Compound Libraries, Diversity Libraries, Europe, Europe, Heterocyclic Chemistry, Medicinal Chemistry, Press Releases | No Comments

KINAXOâ€™s Cellular Target ProfilingÂ® reveals mTOR as a new target of Celebrex

Last Updated on Sunday, 10 May 2009 08:46 Written by admin Sunday, 10 May 2009 08:46

Martinsried, Germany, April 29, 2009 / b3c newswire /Â - Kinaxo Biotechnologies GmbH has successfully applied its Cellular Target ProfilingÂ® technology to identify the protein kinase mTOR as a new cellular target of celecoxib (CelebrexÂ®, Pfizer). Celecoxib is a non-steroidal, anti-inflammatory Cox-2 inhibitor approved for the treatment of osteoarthritis, rheumatoid arthritis and acute pain. In addition, celecoxibâ€™s anti-proliferative effect has earned it a place in numerous clinical trials against several malignancies.

The discovery that celecoxib targets mTOR contributes to a better understanding of the drugâ€™s mode of action and efficacy in cancer patients. mTOR (mammalian target of rapamycin) acts as a central regulator of cell proliferation, cell survival, angiogenesis and cell metabolism. Moreover, mTOR is a key intracellular convergence point for a number of signaling pathways that are abnormally activated in many types of cancer.

As traditional drug development approaches become more and more expensive, drug repositioning has been widely recognized as an opportunity to expand a drugâ€™s therapeutical applications. Here, Cellular Target ProfilingÂ® provides a powerful approach to revealing new targets that indicate additional or alternative medical uses for clinically validated or approved drugs. Further information on celecoxib reprofiling (AN3) and similar studies with other small molecules (e.g. profiling of the natural product geldanamycin, AN2) can be downloaded from our website at www.kinaxo.com.

Link to the news release
http://www.b3cnewswire.com/popup.php?id=149

About KINAXO
Kinaxo Biotechnologies GmbH is a privately-held biotechnology company based in Munich/Martinsried, Germany. We offer advanced chemical proteomics and phosphoproteomics services to support lead compound selection, target deconvolution, drug reprofiling, and off-target toxicity assessment. Kinaxo has several ongoing collaborations, including with Boehringer Ingelheim, Johnson & Johnson and Takeda.

Posted under Cancer Research, Drug Development, Europe, Medicinal Chemistry, Press Releases, Proteomics, Targeted Libraries | No Comments

Richter-Helm and Athera Biotechnologies Partner in Development of Recombinant Protein to Treat Cardiovascular Disease

Last Updated on Friday, 23 January 2009 10:19 Written by admin Friday, 23 January 2009 10:19

Hamburg, Germany and Stockholm, Sweden, January 21st, 2009 — Richter-Helm BioLogics GmbH & Co. KG and Athera Biotechnologies AB have signed an agreement for the development and manufacturing of Atheraâ€™s novel product for prevention of plaque rupture and athero-thrombosis through binding of the protein, Annexin A5, to endothelium. The recombinant protein Annexin A5 is intended for the treatment of patients with Acute Coronary Syndrome and who are at imminent risk for Myocardial Infarction.

This agreement secures a highly cost efficient long-term development and manufacturing plan for Athera, including possible future large volume commercial production. Annexin A5 is a biotechnology product produced using Richter-Helmâ€™s proprietary E. coli based expression system. Richter-Helm will initiate strain and process development of the new process, reaching a 1000 litre production scale.

â€œThe Annexin A5 project fits well with the competence and experience of our company. We are confident that our collaboration will be as efficient and constructive as our negotiations were. Our state-of-the-art facilities are ideal for producing the high-quality Annexin A5 required to comply with the standards of the regulatory agencies.â€, stated Dr. Bert Behnke, Managing Director of Richter-Helm.

â€œWe are very pleased to get Richter-Helm as our development partner, they have an excellent reputation. We have now secured cost competitive and high quality production for clinical and commercial useâ€, said Carina Schmidt, CEO of Athera Biotechnologies.

Posted under Collaborations, Europe, Medicinal Chemistry, Press Releases | No Comments

International symposium “Stem Cell Transplantation in Multiple Sclerosis, October 5th, 2009 Moscow, Russia

Last Updated on Friday, 23 January 2009 11:42 Written by admin Tuesday, 13 January 2009 06:19

International symposium “Stem Cell Transplantation in Multiple Sclerosis: Sharing the Experience” will be heldÂ on October 5th, 2009 inÂ Moscow, Russia. Symposuim Organizers are Pirogov National Medical Surgical Center, National Center for Research and Treatment of Autoimmune Diseases, Russian Cooperative Group for Cellular Therapy, New Jersey Center for Quality of Life and Health Outcomes Research.

The symposium will be the first special meeting fully meant to discuss the state-of-the-art and perspectives of the new and quite promising method of multiple sclerosis treatment – high dose immunosuppressive therapy + autologous hematopoietic stem cell transplantation. It intends to share the newly acquired knowledge in the field, to discuss challenges and perspectives of the method, and to develop collaborative projects. The topics to be covered within the symposium include:
“Â Â Â Regimens of conditioning: Immunoablation or immunosupression?
“Â Â Â Types of transplantation: autologous or allogenic?
“Â Â Â Posttransplant immunological reconstitution
“Â Â Â Side effects
“Â Â Â Outcome measures: clinical, imaging, patient-reported outcomes
“Â Â Â Posttransplant neurorehabilitation
“Â Â Â Long-term follow-up results
“Â Â Â Proposals for cooperative studies

Neurologists, immunologists, transplantologists, hematolosits, specialists in stem cell research are invited to participate in the Symposium.

Key dates:

1 March 2009 -Â Â Deadline for abstract submission
1 April 2009Â Â -Â Â Deadline for early registration

Symposium Organizers Contact Information:

Tel: +7 495 463 4923 or +7 962 710 17 11

Web-site: http://www.stemcellms.ru

Posted under Clinical Trials, Europe, Europe, Medicinal Chemistry, North America, Press Releases | No Comments

Vanderbilt University Announces Partnership with Janssen Pharmaceutica N.V. for Schizophrenia Drug Research

Last Updated on Monday, 12 January 2009 03:46 Written by Editor Monday, 12 January 2009 03:46

Vanderbilt University is pleased to announce a licensing and research agreement with Janssen Pharmaceutica N.V., focusing on discovery of novel drugs for the treatment of schizophrenia. Under the terms of the agreement Vanderbilt University grants Janssen Pharmaceutica N.V. a worldwide exclusive license to existing compounds acting on a neurotransmitter receptor target, and provides a mechanism for the discovery and licensing of additional novel compounds over the next three years.

The licensing and research agreement provides for a total of $10 million in upfront payment and committed research funding to the laboratory of Jeffrey Conn, Ph.D., Director of Vanderbiltâ€™s Program in Drug Discovery. Additional payments will be made based on meeting certain milestones and through royalties on product sales.

Vanderbilt will use its state-of-the-art drug discovery infrastructure, including high throughput screening, medicinal chemistry, molecular biology, and pharmacology testing, to create novel compounds with properties compatible with becoming schizophrenia drugs. In addition to carrying selected compounds from the collaboration into clinical development and through commercialization, Janssen Pharmaceutica N.V. will bring its expertise to the partnership through input on compound design, synthesis and later -stage safety and pharmacokinetic studies.

â€œThis is another milestone for our Program in Drug Discovery and we are excited to be teaming up with one of the worldâ€™s leading developers of drugs for treatment of schizophrenia, said Conn. â€œIt is also a testament to Vanderbiltâ€™s commitment to new approaches to drug discovery and developing new models by which academic institutions work closely with industry partners to deliver new breakthrough medicines that have a fundamental impact on human health.â€

Stef Heylen, M.D., Chief Medical Officer, CNS Research and Early Development at Janssen, said, “Academic collaborations are an important part of our drug discovery strategy. This collaboration underscores the synergies between industry and academia that can help to create solutions for addressing unmet medical needs. It is a great example of how we can work together with academia to better understand complex diseases and hopefully bring improved treatments to patients.”

Posted under Collaborations, Europe, Medicinal Chemistry, North America, Press Releases | No Comments

CytRx Unveils Clinical Development Plan for Pipeline Assets

Last Updated on Friday, 12 December 2008 02:47 Written by Editor Friday, 12 December 2008 02:47

Names World-Renowned Cancer Drug Expert Dr. Joseph Rubinfeld as Chief Scientific Advisor

LOS ANGELES–(BUSINESS WIRE)–CytRx Corporation (NASDAQ: CYTR) today unveiled its corporate strategy to focus its internal resources on the clinical development of oncology drug candidates tamibarotene and INNO-206, which the Company believes offer the greatest mix of near-term and medium-term revenue potential among its clinical assets. CytRx will pursue partnerships to advance the clinical development of INNO-406 (bafetinib) and its clinical molecular chaperone portfolio, where it continues to see significant future revenue potential. The Company further intends to use its proprietary high-throughput, high-content drug screening Master Chaperone Regulator Assay (MaCRA) platform to discover additional molecular chaperone drug candidates, including those that may inhibit cancer growth, which will support internal efforts to build an oncology drug franchise or future out-licensing possibilities.

CytRx also announced that Board of Directorsâ€™ member Dr. Joseph Rubinfeld has accepted the additional responsibility of Chief Scientific Advisor, and will consult on all aspects of the Companyâ€™s oncology development programs while serving as an important interface between the Company and investors, clinicians and industry thought leaders. Dr. Rubinfeld brings substantial expertise in oncology and drug development through his distinguished career. Dr. Rubinfeld was employed at Bristol-Myers Company International Division as Vice President and Director of Research and Development. While at Bristol-Myers, Dr. Rubinfeld was instrumental in licensing the original anticancer line of products, including Mitomycin and Bleomycin. Among other accomplishments, he was among the four co-founders of Amgen, Inc., and founded SuperGen, Inc., where he previously served as CEO, President and Chief Scientific Officer. In his career he has been instrumental in the development of several blockbuster cancer drugs including cisplatinum, etoposide, erythropoietin, decibitene and pentostatin, and the antibiotics amoxicillin and cefadroxil.

Steven A. Kriegsman, CytRx President and CEO said, â€œWe feel that our stockholders are best served by a focus on potential therapeutics for cancer. We believe tamibarotene has strong potential as a revenue generator with a high likelihood for rapid U.S. approval as a third-line treatment for acute promyelocytic leukemia (APL). Our view is based on the substantial clinical history of tamibarotene as an approved treatment of relapsed APL, in Japan and the existing special protocol assessment (SPA) in place with the U.S. Food and Drug Administration (FDA) for our ongoing U.S. registration clinical trial. We are accelerating enrollment in this clinical trial, with the expectation of filing an NDA with the FDA as early as 2010. We are also taking steps to move into a Phase 2 clinical trial with INNO-206, our highly promising targetable pro-drug for the commonly prescribed chemotherapeutic doxorubicin. We believe that INNO-206 could be effective in a wide variety of cancers, including small cell lung cancer, sarcoma, breast and ovarian cancer and Non-Hodgkins Lymphoma.

â€œImportantly, we expect that we have ample financial resources with our current cash position and investment in RXi Pharmaceuticals Corporation to support this strategy,â€ according to Mr. Kriegsman. â€œWe have strong oncology expertise within CytRx and are delighted that Dr. Joseph Rubinfeld, our long-time board member who has enjoyed an illustrious career developing cancer drugs, will be taking a leadership role in our oncology programs.â€

Dr. Rubinfeld said, â€œHaving reviewed the extensive data on tamibarotene and INNO-206, I am excited about the potential for these two cancer drug candidates and look forward to working closely with the CytRx management team to advance their clinical development to potential commercialization. I am also encouraged by the Phase 1 data we announced earlier this month with INNO-406, now known as bafetinib, which demonstrated positive, clinical responses in 35% of patients with refractory chronic myeloid leukemia. I believe these results will be instrumental in our search for a partnership for bafetinib.â€

Mr. Kriegsman added, â€œWe also stand behind our view that our orally administered molecular chaperone drug candidates, arimoclomol and iroxanadine, provide enormous potential in addressing large, underserved markets and are convinced that the prudent course to maximize stockholder value in this economic climate is to pursue pharmaceutical partners to share additional development costs for these longer-term programs. We intend to complete our ongoing arimoclomol animal toxicology studies and work aggressively toward lifting the current clinical hold in order to enable this drug candidate to move back into the clinic. At that point, we will seek partners for further development of arimoclomol as a therapeutic treatment for both ALS and stroke recovery. Additionally, iroxanadine has shown significant potential as a therapeutic treatment for diabetic foot ulcers and other diabetic complications, and based on Phase 2 data, we will pursue potential partnerships in cardiovascular conditions.â€

CytRxâ€™s drug portfolio includes the following:

Oncology Drug Candidates:

Tamibarotene: CytRx holds the North American and European rights to tamibarotene, a rationally designed, synthetic retinoid compound designed to potentially avoid toxic side effects of the current first-line APL treatment trans-retinoic acid (ATRA). CytRx is actively enrolling patients in a Phase 2 registration clinical trial, known as STAR-1, with tamibarotene to evaluate its efficacy and safety as a third-line treatment for APL. The registration study is being conducted under a Special Protocol Assessment. The FDA has granted Orphan Drug Designation and Fast Track Designation for the use of tamibarotene in patients with relapsed or refractory APL following treatment with ATRA and arsenic trioxide.

There are currently no approved third-line treatment options for refractory APL patients. CytRx estimates the U.S. market opportunity for tamibarotene in refractory APL at approximately $20 million annually. CytRx scientists are also evaluating clinical strategies for developing tamibarotene as a first-line or second-line APL therapy. The estimated annual market potential in the U.S. and Europe for an expanded label including refractory, maintenance and front-line therapy is $150 million. CytRx also retains an option to expand its licenses for the use of tamibarotene in other cancers including multiple myeloma, myelodysplastic syndrome and certain solid tumors in the U.S., and multiple myeloma, myelodysplastic syndrome and solid tumors, other than hepatocellular carcinoma, in Europe.

INNO-206: This pro-drug derivative of the commonly prescribed chemotherapeutic agent doxorubicin is designed to reduce adverse events by controlling drug release and preferentially targeting the tumor. In a Phase 1 study, INNO-206 was administered in doses at up to six times the standard dosing of doxorubicin without an increase in observed side effects over those historically seen with doxorubicin. Objective clinical responses were seen in patients with sarcoma, breast and lung cancers. The Company plans to evaluate further clinical development of INNO-206 in a wide variety of cancers, including sarcomas, breast and ovarian cancer, and Non-Hodgkins Lymphoma.

INNO-406 (bafetinib): INNO-406 (bafetinib), a potent, orally available, rationally designed, dual Bcr-Abl and Lyn-kinase inhibitor, is being evaluated for the treatment of patients with chronic myeloid leukemia (CML) and other leukemias that have a certain mutation called the Philadelphia Chromosome (Ph+) and are intolerant of or resistant to imatinib (Gleevec^Â®) and second-line tyrosine kinase inhibitors (i.e. dasatinib (Sprycel^Â®) and nilotinib (Tasigna^Â®)). In November 2008, CytRx announced that bafetinib demonstrated positive, clinical responses in 35% of patients with CML in Phase 1 clinical testing. The Phase 1 clinical trial was used to determine the optimal dose prior to Phase 2 clinical efficacy testing.

CML is a type of cancer that starts in blood-forming cells of the bone marrow and invades the blood. In 2007, the American Cancer Society estimated that approximately 4,600 new cases of CML were diagnosed in the U.S. and that the number will increase as the population ages. Current estimates are that worldwide CML prevalence will increase by 10,000 patients a year, reaching a population of 110,000 in 2010. The global market will grow to an estimated $5.5 billion by 2012.

Molecular Chaperone Regulation

CytRx is a leader in molecular chaperone regulation technology. The Company currently has two orally administered, clinical-stage, drug candidates and recently discovered a series of additional compounds that may provide a pipeline for additional drug candidates. The Company’s drug candidates are believed to function by regulating a normal cellular protein repair pathway through the activation or inhibition of “molecular chaperones.” Because damaged proteins are thought to play a role in many diseases, activation of molecular chaperones that help to reduce the accumulation of misfolded proteins may have therapeutic efficacy in a broad range of disease states. Similarly, CytRx believes that the inhibition of molecular chaperones that normally help protect cancer cells from toxic misfolded proteins may result in the selective destruction of cancer cells.

Arimoclomol: This molecular chaperone regulator drug candidate is being considered as a treatment for amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) and stroke recovery. Arimoclomol has been studied in seven Phase 1 and two Phase 2 clinical trials without any significant adverse events. CytRxâ€™s Phase 2b clinical trial with arimoclomol as a treatment for ALS was placed on clinical hold by the FDA in January 2008, unrelated to any data generated by human studies, and additional preclinical toxicology studies are underway to resolve this issue.
Iroxanadine: CytRx believes that this orally available small molecule compound represents a potentially powerful breakthrough in the treatment of vascular diseases that are caused in part by damage to “vascular endothelium” that lines the inside of blood vessels. CytRx believes that endothelial dysfunction plays a key role in the development of various vascular diseases or their complications including diabetic ulcers, thrombosis, retinopathy, and peripheral artery disease. Preclinical and clinical studies with iroxanadine indicate that it has therapeutic potential for the treatment of cardiovascular atherosclerosis. According to the National Heart, Lung & Blood Institute, atherosclerosis is a leading cause of illness and death in the U.S. and affects approximately 4.6 million people annually.

CytRx San Diego Laboratory: The CytRx San Diego Laboratory is using the Companyâ€™s proprietary Master Chaperone Regulator Assay (MaCRA), a cell image-based screening tool that enables the rapid and quantifiable screening of large numbers of small molecule compounds. This technology is used to identify potential drug candidates that modify the activity of a protein known as heat shock transcription factor 1 (Hsf1) and consequently control entire groups of molecular chaperone proteins that repair or degrade toxic misfolded proteins present in diseased cells. Evaluation of the compounds identified in the screen has shown that they exhibit cytoprotective properties in cell culture models of disease. This platform has broad applicability to a range of therapeutic areas, through its ability to identify drug candidates that can either inhibit or amplify molecular chaperone activity. Information related to the development of MaCRA for compound screening was published in the November 2008 issue of the peer-reviewed Journal of Biomolecular Screening.

CytRx Oncology Expertise

Collectively, CytRx’s management and its Board of Directors have brought numerous cancer drugs to market. In addition to Dr. Rubinfeld, the senior managers and directors of CytRx who hold significant oncology experience include: Max Link, Ph.D., Chairman of the Company’s Board of Directors since 1996, who served for a number of years as Chairman and CEO of Sandoz Pharma as well as a director of Alexion Pharmaceuticals, Inc., Celsion Corporation and Discovery Laboratories, Inc.; Jack R. Barber, Ph.D., Chief Scientific Officer, who has significant R&D experience in oncology at Immusol and Viagene, where he most recently served as Head of Oncology; and Shi Chung Ng, Ph.D., Senior Vice President of Research and Development, who has substantial R&D experience at companies such as Abbott and ArQule, Inc., and most recently served as Vice President of Molecular Oncology at Ligand Pharmaceuticals.

About CytRx Corporation

CytRx Corporation is a biopharmaceutical research and development company engaged in the development of high-value human therapeutics. The CytRx drug development pipeline includes programs in clinical development for cancer indications, including tamibarotene in a registration study for the treatment of acute promyelocytic leukemia (APL). CytRx is developing two drug candidates based on its industry-leading molecular chaperone technology, which aims to repair or degrade misfolded proteins associated with disease. The Company owns and operates a research and development facility in San Diego. CytRx also maintains a 45% equity interest in publicly traded RXi Pharmaceuticals, Inc. (NASDAQ: RXII). For more information on the Company, visit www.cytrx.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Such statements involve risks and uncertainties that could cause actual events or results to differ materially from the events or results described in the forward-looking statements, including risks relating to the outcome or results of any pre-clinical or clinical testing of CytRx’s potential oncology or molecular chaperone drug candidates, including tamibarotene as a third-line treatment for APL, risks related to CytRxâ€™s ability to enter into partnerships to advance the clinical development of INNO-406 and its clinical molecular chaperone portfolio, uncertainties related to the impact of the FDA’s clinical hold on the Company’s arimoclomol clinical trial for ALS on the timing and ability to resume clinical testing at the desired dosage of arimoclomol, the risk that any requirements imposed on the Company’s planned clinical trial designs for ALS or stroke recovery by the FDA as a result of the concerns expressed in their clinical hold of the Company’s ALS program might adversely affect the Company’s ability to demonstrate that arimoclomol is efficacious in treating ALS or stroke patients or cause the Company to cancel one or both of those trials, risks related to CytRx’s need for additional capital or strategic partnerships to fund its ongoing working capital needs and development efforts, risks related to the future market value of CytRx’s investment in RXi and the liquidity of that investment, and the risks and uncertainties described in the most recent annual and quarterly reports filed by CytRx with the Securities and Exchange Commission and current reports filed since the date of CytRx’s most recent annual report. All forward-looking statements are based upon information available to CytRx on the date the statements are first published. CytRx undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Posted under Cancer Research, Clinical Trials, Compound Screening, Discoveries, Innovations and Patents, Drug Development, FDA News, Medicinal Chemistry, New Drugs, New Products, North America, Oncology Research, Press Releases, R & D, Research Projects, USA and Canada | No Comments

MorphoSys and Galapagos Enter Alliance to Co-develop Novel Therapeutic Antibodies in Bone and Joint Disease

Last Updated on Monday, 1 December 2008 12:59 Written by Editor Monday, 1 December 2008 12:59

Combination of Proprietary Drug Targets and Unique Technologies to Create Range of New Therapeutic Antibodies

MUNICH, GERMANY — (Marketwire) — 11/26/08 — MorphoSys AG (FSE: MOR; Prime StandardSegment, TecDAX) and Galapagos NV (Euronext: GLPG) announced today the launch of a long term co-development alliance aimed at discovering and developing antibody therapies based on novel modes of action in bone and joint disease, including rheumatoid arthritis, osteoporosis and osteoarthritis.

The alliance spans all activities from target discovery through to completion of proof of concept clinical trials of novel therapeutic antibodies. Both companies will contribute their core technologies and expertise to the alliance. Galapagos will provide antibody targetsimplicated in bone and joint disease in addition to its adenoviral target discovery platform to discover further targets for antibody development.MorphoSys will contribute its HuCAL antibody technologies to generate fully human antibodies directed against these targets. The initial goal is to further validate the targets through disease-specific in vitro and in vivotesting of the antibodies. After successful validation, the alliance will select antibody programs for pre-clinical and clinical development.Following proof of concept in human clinical trials, programs will be partnered for subsequent development, approval and marketing.

Under the terms of the agreement, Galapagos and MorphoSys will share the research and development costs, as well as all future revenues equally.Decisions will be made by a Joint Steering Committee comprising members of both companies. An initial set of three targets implicated in bone and joint disease has been selected for the collaboration, and Galapagos isalready commencing with production of these proteins for the alliance.Generation of antibodies directed against these targets will start in2009. More targets will be selected using Galapagos’ target discovery platform to fuel the alliance in the coming years. If successful, the first antibody programs based on these novel targets could enter the clinic within four to five years.

“With this alliance, we are adding a biologics strategy to our small molecule drug discovery. Galapagos is the world leader in discovery ofnovel targets, and this alliance with MorphoSys enables us to explore the potential of proprietary antibody targets. Antibody approaches have provento be successful in developing new therapies for major diseases, including rheumatoid arthritis. Having both approaches, small molecules andantibodies, to fill our product pipeline in bone and joint disease willfurther establish Galapagos as the leader in this field,” said Onno van deStolpe, Chief Executive Officer of Galapagos. “With our cash position and revenue streams from both BioFocus DPI and our pharma alliances, we are in a good financial position to enter into this alliance to create value for our shareholders.”

“This alliance represents a major step in our efforts to gain access to novel antibody targets for proprietary drug development in disease areas with a high unmet medical need. The partnership with Galapagos combines both the scientific and financial strength of two leading companies in their space,” said Dr. Simon Moroney, Chief Executive Officer of MorphoSys. “We are excited to combine our broad antibody expertise with Galapagos’ target discovery capabilities and disease know-how to form a successful partnership. The access to novel disease-related target molecules from a renowned partner accelerates the expansion of our proprietary antibody pipeline. This alliance also complements our development efforts in the field of inflammation and arthritis includingour lead program MOR103.”

With this strategic alliance, MorphoSys gains access to a proven target discovery engine as well as to Galapagos’ expertise in bone and joint disease, to support its therapeutic antibody pipeline expansion. The threemain indications of bone and joint disease – rheumatoid arthritis,osteoporosis and osteoarthritis – all represent very significant marketopportunities with several million people affected worldwide and combinedsales of drug treatments of more than US$ 15 billion in 2006.

Through the alliance with MorphoSys, Galapagos enters the rapidly growingmarket for therapeutic antibodies. In 2007, total sales for the 20antibody drugs on the market amounted to more than US$ 25 billion andantibody sales are forecast to increase to approximately US$ 50 billion in 2013. Fully human antibodies are recognized as the next generation and the majority of therapeutic antibodies currently in development are humanized or fully human. The average industry timescale from discovery to pre-clinical development of antibody therapies is only two to three years, considerably shorter than the average six years for small molecules.Antibodies also incur lower attrition rates than small molecules.

Galapagos and MorphoSys will conduct a conference call and live audio webcast today at 02:00 p.m. CET (8:00 a.m EST) to provide detailed information on the alliance.Dial-in number for the Conference Call (listen-only):Germany & U.K. residents: +32 2 401 53 06For U.S. residents: +1 866 931 1567 Please dial in 10 minutes before the beginning of the conference.Approximately two hours after the press conference, the archived webcast will be available for replay of the conference on http://www.morphosys.comand http://www.glpg.com.

For further information please contact: Dr. Claudia Gutjahr-LÃ¶ser, Head ofCorporate Communications & Investor Relations, Tel: +49 (0) 89 / 899 27-122, gutjahr-loeser@morphosys.com or Mario Brkulj, Manager CorporateCommunications & Investor Relations, Tel: +49 (0) 89 / 899 27-454,brkulj@morphosys.com

About Galapagos:

Galapagos (Euronext Brussels: GLPG; Euronext Amsterdam: GLPGA; OTC: GLPYY)is a drug discovery company with pre-clinical programs in bone and jointdiseases and bone metastasis. Its BioFocus DPI division offers a fullsuite of target-to-drug discovery products and services to pharmaceuticaland biotech companies, encompassing target discovery and validation,screening and drug discovery through to delivery of pre-clinicalcandidates. BioFocus DPI also provides adenoviral reagents for rapididentification and validation of novel drug targets, compound libraries fordrug screening as well as chemogenomics and ADMET database products toselect targets and compounds. Galapagos currently employs about 450 peopleand operates facilities in six countries, with global headquarters inMechelen, Belgium. More information about Galapagos and BioFocus DPI canbe found at www.glpg.com and www.biofocusdpi.com.

About Galapagos’ target discovery technology:

Galapagos’ target discovery engine is based on adenoviruses thatefficiently introduce human gene sequences into a wide variety of humancells to knock-down specific proteins. High-throughput assays thatrepresent a selected human disease state are then used to functionallyselect for those proteins that have a causative effect in those models ofhuman disease. After rigorous validation of these protein targets, theyform the basis for the development of novel drugs.

About MorphoSys:

MorphoSys is a publicly traded biotechnology company focused on thegeneration of fully human antibodies as a means to discover and developinnovative antibody-based drugs against life-threatening diseases.MorphoSys’s goal is to establish HuCAL as the technology of choice forantibody generation in research, diagnostics and therapeutic applications.The Company currently has therapeutic and research alliances with themajority of the world’s largest pharmaceutical companies includingBoehringer Ingelheim, Centocor/Johnson & Johnson, Novartis, Pfizer andRoche. Within these partnerships, more than 50 therapeutic antibodyprograms are ongoing in which MorphoSys participates through exclusivelicense and milestones payments as well as royalties on any end products.Additionally, MorphoSys is active in the antibody research market throughits AbD Serotec business unit. The business unit has operations in Germany(Munich), the U.S. (Raleigh, NC) and U.K. (Oxford). For further informationplease visit http://www.morphosys.com/

HuCALÂ® and HuCAL GOLDÂ® are registered trademarks of MorphoSys AG

Posted under Business and Investment, Clinical Trials, Collaborations, Discoveries, Innovations and Patents, Drug Development, Europe, Industry News, Medicinal Chemistry, New Drugs, News by Region, News by Subject, North America, Press Releases | No Comments

The difficulties of Cushingâ€™s syndrome

Last Updated on Wednesday, 26 November 2008 01:55 Written by Editor Wednesday, 26 November 2008 01:55

Diagnosing and treating Cushingâ€™s syndrome is sometimes just as difficult as it was 70 years ago.

For as long as it has been described, Cushingâ€™s syndrome has presented physicians with a problem. Harvey Cushing first described it in 1932, and the diagnosis, differential diagnosis and treatment of Cushingâ€™s have remained a major challenge for endocrinologists ever since.

Though uncommon, it is difficult to consider Cushingâ€™s syndrome a rare occurrence. New research has shown Cushingâ€™s syndrome to have a substantially higher prevalence than previously thought. Unexpected endogenous hypercortisolism may occur in 0.5% to 1% of patients with hypertension, 2% to 3% with poorly controlled diabetes, 6% to 9% with incidental adrenal masses and 11% with osteoporosis and vertebral fractures.

â€œWe are gaining an appreciation that Cushingâ€™s is more common than it was once believed to be,â€ said Mary Ruppe, MD, endocrinologist at the University of Texas Health Science Center at Houston, and program committee chair of the Women in Endocrinology organization. â€œThis fact points to the need for data regarding the value of the different diagnostic approaches and for data regarding treatment/outcomes in populations with Cushingâ€™s.â€

As most of the characteristics of Cushingâ€™s are common in the general population, including obesity, depression and hypertension, it is extremely difficult for endocrinologists to decide on who should be screened for the disorder. A recent clinical review by Hershel Raff, PhD, and James W. Findling, MD, noted that as the number of patients in these high-risk groups continues to increase, the need for a sensitive and specific diagnostic test for Cushingâ€™s syndrome has become paramount.

The three most commonly performed diagnostic studies for Cushingâ€™s syndrome â€” urine-free cortisol, low-dose dexamethasone suppression test and the nocturnal salivary cortisol â€” are also not without hurdles. All three have been shown to produce false positives and false negatives.

Approximately 80% of patients with Cushingâ€™s syndrome have an adrenocorticotropic-secreting neoplasm from a pituitary tumor (Cushingâ€™s disease) or a nonpituitary neoplasm, and the treatment of Cushingâ€™s disease remains challenging for both endocrinologists and neurosurgeons as well. Transsphenoidal surgery is currently the standard treatment of choice in patients, but achieving surgical remission has been difficult as well.

â€œCushingâ€™s syndrome is a very rare but important diagnosis for the patient and endocrinologist. Confirming the diagnosis may be challenging, and before embarking on a costly set of tests, the endocrinologist should be reasonably assured that the patient indeed requires diagnostic exclusion by rigorous screening methods,â€ said Shlomo Melmed, MD, senior vice president of Academic Affairs at Cedars Sinai Medical Center, Los Angeles, and an Endocrine Today editorial board member

With more than 7.5 decades of research since Dr. Cushingâ€™s discovery, what are the best methods of diagnosis and treatment for Cushingâ€™s syndrome? Endocrine Today talked with leading researchers in the field to uncover the current trends in Cushingâ€™s syndrome treatment.

Screening process

Laurence Katznelson, MD, associate professor of medicine and neurosurgery at Stanford University, and medical director of the pituitary program at Stanford Hospital and Clinics, explained to Endocrine Today the difficulty of deciding who should be screened for Cushingâ€™s syndrome. For instance, although the syndrome is associated with multiple comorbidities, including obesity, hypertension and depression, endocrinologists should be prepared to delve a little deeper into the symptoms to see if they warrant a screening test.

â€œThe presence of Cushingâ€™s syndrome should be considered if these medical conditions are present, though diagnostic testing should be performed only in subjects who have signs favoring Cushingâ€™s, such as demonstration of objective proximal weakness, spontaneous ecchymoses and violaceous striae,â€ Katznelson said.

â€œFor example, central obesity with supraclavicular and dorsicervical fat pads would favor a diagnosis of Cushingâ€™s syndrome, in contrast to the presence of generalized obesity,â€ he said.

Raff and Findling noted in a recent clinical review that endogenous cortisol excess also leads to fairly specific catabolic effects â€” including the thinning of the skin with easy bruising, abdominal striae, poor wound healing, immune suppression, rib fractures, hirsutism in women, acne and muscle wasting leading to proximal muscle weakness.

â€œThere is no clear guideline,â€ said Roberto Salvatori, MD, associate professor of medicine in the division of endocrinology at Johns Hopkins University School of Medicine. â€œYou need to keep your mind open.â€

â€œSometimes Cushingâ€™s is obvious. Sometimes, when it is mild, it may not be diagnosed for many years. One must screen a lot of patients to find one with Cushingâ€™s. However, anytime a physician thinks about the possibility of a patient having the disease, work-up should be initiated,â€ he said.

Testing options

Opinions varied when Endocrine Today asked researchers which of the three tests for Cushingâ€™s syndrome was most reliable.

â€œNo test is 100% sensitive or specific,â€ Salvatori said. â€œI always use two, sometimes three, screening tests.â€ However, Salvatori noted he feels the night-time salivary cortisol test is the most reliable and easy to obtain.

Raff and Findling described the measurement of free cortisol in a 24-hour urine collection as being long considered the gold standard for the diagnosis of endogenous hypercortisolism. The test relies on the concept that as daily production of cortisol is increased, the free cortisol filtered and not reabsorbed or metabolized in the kidneys will be increased. They noted that current research has shown that many patients with mild Cushingâ€™s syndrome do not have elevations of urine-free cortisol, â€œmaking it a poor screening test for this condition.â€

The low-dose dexamethasone suppression test relies on the concept that the correct dose of dexamethasone will suppress ACTH, and cortisol will release in normal patients while patients with corticotroph adenomas will not suppress below a specified cut off. Raff and Findling noted that because of the significant variability of the biological behavior of corticotroph adenomas, research has shown that neither the overnight 1-mg dexamethasone suppression test nor the two-day low-dose dexamethasone suppression test appears to be reliable using the standard cutoffs for serum cortisol.

According to Raff and Findling, there is no diagnostic test used in the evaluation of Cushingâ€™s syndrome that performs better than the late night/midnight salivary cortisol method. The concept is based on the fact that patients with mild Cushingâ€™s syndrome fail to decrease cortisol secretion to its nadir at night. However, they still acknowledged that many factors, such as stress, sleep disturbances and psycho-neuroendocrine may falsely elevate nocturnal cortisol secretion.

â€œBecause each of these tests has associated false positives and negatives, a combination of these tests is often necessary for a valid diagnosis,â€ Katznelson said. â€œIn the end, these tests need to be considered in the context of a history and physical examination that favors this diagnosis.â€

Lynette Nieman, MD, associate director of the Intramural Endocrinology Training Program at the NIH, agreed. â€œOf the three recommended tests, each is useful in certain conditions,â€ she said. â€œI try to stress that the testing should be individualized since some tests are likely to be falsely positive in some situations, eg, a woman on birth control pills is likely to have a high corticosteriod-binding globulin, which might elevate serum cortisol.â€

Ruppe said the choice between the tests should be based on patient characteristics that will allow for adequate collection of each sample. â€œFor instance, the use of a late-night salivary cortisol measurement would be suboptimal in an individual who works the third shift and may not have an intact circadian rhythm, or the choice of a 24-hour urinary free cortisol may be suboptimal in an individual with urinary frequency or urinary incontinence.â€

Ruppe also noted that one possible improvement would be to improve standardization of the assays across different labs. â€œSince there is no standardization, the quality of the performance of the assay can vary across different facilities and centers,â€ she said.

Petrosol sinus sampling

Another controversial topic in the field is whether or not the inferior petrosol sinus should be sampled for an ACTH gradient to distinguish between Cushingâ€™s disease and occult ectopic ACTH syndrome.

The invasive procedure has proven to be relatively safe when performed by experienced radiologists, but not all medical centers have the capability.

A woman with mild hypercortisolism, a normal or slightly elevated plasma ACTH and normokalemia has an approximately 95% likelihood of having Cushingâ€™s disease before any differential diagnostic testing is performed, according to Raff and Findling. In contrast, a male patient with prodigious hypercortisolism of rapid onset, hypokalemia and marked elevations of plasma ACTH may be more likely to have an occult ectopic ACTH-secreting tumor.

About half of patients with ACTH-secreting microadenomas are estimated to have a normal pituitary MRI. In such situations, it is important to perform further testing, particularly an inferior petrosal sinus catheterization, to discern the presence of an ectopic ACTH-producing lesion, according to Katznelson.

â€œSome people would say that every patient should have it because it is the one best test for the differential diagnosis of ACTH-dependent Cushingâ€™s syndrome,â€ Nieman said. â€œHowever, patients in whom data strongly suggest Cushingâ€™s disease might forego it.â€

â€œIn a young woman with an MRI with a definitive adenoma and high-dose dexamethasone test showing less than 60% suppression, it is reasonable to proceed with surgery,â€ Salvatori said. â€œBut even the International Prostate Symptom Score is not 100% sensitive or specific.â€ Raff said that he disagrees with the high-dose dexamethasone test.

Fast Facts: Issues at Hand

Transsphenoidal surgery

Currently, transsphenoidal surgery is the primary treatment of Cushingâ€™s disease associated with an ACTH-secreting pituitary tumor. According to recent studies, remission rates after transsphenoidal pituitary microsurgery range from 42% to 86%.

Raff told Endocrine Today that the most important treatment recommendation that an endocrinologist makes to a patient with Cushingâ€™s disease is referral to a neurosurgeon with extensive experience.

â€œReferral to a neurosurgeon who is highly experienced in this procedure is critical,â€ Katznelson agreed. He noted that there have been studies demonstrating that both the degree of tumor bulk resection and rates of biochemical remission are increased for all types of pituitary tumors when the surgery is performed by a neurosurgeon with extensive experience in endonasal pituitary surgery.

â€œIn Cushingâ€™s disease, this is especially true,â€ Katznelson said. â€œBecause the tumors in this disorder are often small, if not microscopic, the surgical strategy may require dissection through the gland. In inexperienced hands, this may result in higher rates of hypopituitarism and lower rates of biochemical cure,â€ Katznelson said.

â€œThere is no doubt that the surgeonâ€™s experience influences the success rate,â€ Nieman said.

Constantine Stratakis, MD, with the National Institute of Child Health and Human Development, said he agreed, and stressed the importance of confirmation of diagnosis of Cushingâ€™s syndrome prior to a referral to a neurosurgeon.

â€œThere is nothing worse than an inexperienced surgeon operating on a patient with Cushingâ€™s or a surgeon operating on a patient who does not have a firm diagnosis of Cushingâ€™s syndrome,â€ Stratakis said.

â€œSurgery offers a reasonable chance for cure in the hands of an experienced neurosurgeon,â€ said Amir Hamrahian, MD, a staff physician at the Endocrinology Institute at the Cleveland Clinic. â€œWe are currently involved in two studies looking at new medications for medical treatment of patients with Cushingâ€™s syndrome. However, surgery is still the best initial approach for those not cured,â€ Hamrahian said.

The future

â€œMedications are the future for patients with inoperable, recurrent Cushingâ€™s syndrome,â€ Stratakis said, referring to pasireotide (SOM230), a somatostatin analog.

He was part of a study in 2006 examining the in vitro effects of SOM230 on cell proliferation in human corticotroph tumors. Researchers found SOM230 significantly suppressed cell proliferation and ACTH secretion in primary cultures of human corticotroph tumors. They concluded that SOM230 may have a role in the medical therapy of Cushingâ€™s disease. Raff said he believes that clinical trials in patients with Cushingâ€™s disease who used SOM230 were not particularly successful. Anne Klibanski, MD, director of the neuroendocrine clinical center at Massachusetts General Hospital and primary investigator of the study, commented that in vitro studies play a critical role in assessing novel targeted pituitary tumor therapies. It is only in rigorous clinical trials that the overall efficacy and risks of such therapies can be established, she suggested.

Constantine Stratakis, MD

â€œMicrosurgical improvements will also be significant, but the major problem right now is the number of patients who are left untreated with recurrent disease,â€ Stratakis said. â€œFor them, there are very few options other than irradiation, so innovative medical treatments with molecularly designed compounds or targeted to specific receptors and/or functions of the pituitary are the most important advances that I see coming in the near future,â€ Stratakis said.

According to James Liu, MD, assistant professor of neurologic surgery at Northwestern University Feinberg School of Medicine in Evanston, Ill., the future appears bright in the battle against Cushingâ€™s.

â€œTechnical advances in surgery including endoscopic pituitary surgery and pseudocapsular dissection can improve surgical outcomes,â€ Liu said.

Katznelson said he hopes the future will bring improved diagnostic strategies important for detecting true Cushingâ€™s syndrome in the presence of multiple comorbidities. He noted that the ongoing research studies involving innovative medical therapeutic strategies that target the corticotroph adenoma itself, or block the effects of cortisol in the periphery, should bring new treatment options in the future.

â€œThese studies will hopefully lead to novel medical options for this syndrome,â€ Katznelson said. â€œThere have been significant advances in surgery, particularly with the development of minimally invasive, endoscopic surgery that has resulted in both improved biochemical outcomes and patient tolerability.â€ â€“ by Angelo Milone

For more information:

* Aron DC, Raff H, Findling JW. Effectiveness vs. efficacy: the limited value in clinical practice of high-dose dexamethasone suppression testing in the differential diagnosis of ACTH-dependent Cushingâ€™s syndrome. J Clin Endocrinol Metab. 1997:82;1780-1785.

* Batista DL, Zhang X, Gejman R, et al. The effects of SOM230 on cell proliferation and ACTH secretion in human corticotroph pituitary adenomas. J Clin Endocrinol Metab.2006;91:4482-4488.

* Carroll T, Raff H, Findling JW. Late-night salivary cortisol measurement in the diagnosis of Cushingâ€™s syndrome. Nat Clin Pract Endocrinol Metab. 2008;4:344-350.

* Findling JW, Raff H. Cushingâ€™s syndrome: Important issues in diagnosis and management. J Clin Endocrinol Metab. 2006;91:3746-3753

* Liu JK, Fleseriu M, Delashaw Jr. JB, et al. Treatment options for Cushingâ€™s disease after unsuccessful transsphenoidal surgery. Neurosurg Focus. 2007;23:E8.

* Nieman L. The dexamethasone-suppresssed corticotropin-releasing hormone test for the diagnosis of Cushingâ€™s syndrome: What have we learned in 14 years? J Clin Endocrinol Metab. 2007;92:2876-2878.

* Lad SP, Patil CG, Laws ER Jr, Katznelson L. The role of inferior petrosal sinus sampling in the diagnostic localization of Cushingâ€™s disease. Neurosurg Focus. 2007:23:E2.g

Posted under Clinical Trials, Cushingâ€™s syndrome, Education, Industry News, Medicinal Chemistry, News by Region, News by Subject, North America, Press Releases, Research Projects | No Comments

GEN Reports on the Trend Toward Predictive Toxicogenomics

Last Updated on Thursday, 20 November 2008 01:00 Written by Editor Thursday, 20 November 2008 01:00

NEW ROCHELLE, N.Y., Nov 19, 2008 /PRNewswire via COMTEX/ — Biotech scientists increasingly are applying genomics technologies to toxicology research to better understand the effects of novel drug candidates on a variety of organ systems, reports Genetic Engineering & Biotechnology News (GEN). They are especially interested in figuring out a new compound’s mechanism of action and eventually developing a predictive toxicology technique, according to the November 15 issue of GEN. ( http://www.genengnews.com/articles/chitem.aspx?aid=2675)

“Toxicogenomics, which is essentially gene-expression profiling, is the next step up from basic toxicology studies,” says John Sterling, Editor-in-Chief of GEN. “It is a more complex approach, and it will take some time before it becomes a regular tool in the technology armentarium of drug discovery and pharmaceutical scientists.”

So far most companies are focusing on toxicogenomics primarily as a method to explore mechanisms of action rather than to predict toxicity. Roche, for example, uses toxicogenomics to generate hypotheses when trying to unravel the cellular machinery underlying toxicity responses, which then are tested more thoroughly using other assays. Novartis is employing known toxic compounds to develop the techniques to understand the mechanistic actions of toxicity. Such screening led to the recent validation of biomarkers for kidney toxicity.

Groups such as The C-Path Predictive Safety Testing Consortium are examining published toxicogenomics multiple gene biomarkers or signatures and trying to validate those signatures across laboratories.

Also covered in the GEN article is work being carried out by Amgen, Entelos, Lilly Research Laboratories, Hamner Institutes for Health Sciences, and the Health and Environmental Sciences Institute.

SOURCE Genetic Engineering & Biotechnology News

Posted under Compound Screening, Discoveries, Innovations and Patents, Drug Development, Genomics & Pharmacogenomics, Industry News, Medicinal Chemistry, News by Region, News by Subject, North America, Press Releases | No Comments

WuXi PharmaTech Inks New Three-year Deal with Pfizer

Last Updated on Tuesday, 11 November 2008 02:55 Written by admin Tuesday, 11 November 2008 02:55

WuXi PharmaTech (NYSE: WX) has signed a new three-year CRO deal with Pfizer (NYSE: PFE) to collaborate on in vitro ADME (Absorption, Distribution, Metabolism and Excretion) services. Although WuXi has already been providing the services to Pfizer, WuXi said the new agreement â€œstrengthens an already productive relationship.â€ WuXi also provides Pfizer with synthetic chemistry, parallel medicinal chemistry (PMC), and bioanalytical services.

In partnership with Pfizer, WuXi PharmaTech will establish ADME assays to provide in vitro screening services on compounds WuXi PharmaTech synthesizes for Pfizer. The goal is to improve the pharmacokinetic properties of new compounds.

The announcement did not disclose financial details of the contract.

Posted under ADMET Studies, Collaborations, Compound Libraries, Compound Screening, Drug-Like Compounds, Medicinal Chemistry, North America, Press Releases | No Comments

Drug Discovery Latin America, February 26-27, 2009 – Rio de Janeiro, Brazil

Last Updated on Friday, 24 October 2008 11:25 Written by admin Friday, 24 October 2008 11:25

The inaugural Drug Discovery Latin America conference and exhibition will be held in the colourful city of Rio de Janeiro in the days immediately following the world famous carnival.

The purpose of this meeting is to review the status of drug discovery activities in Latin America and to assist its future development. Business and research leaders from both developed markets and BRIC countries will bring their knowledge and experience to share. Participants will be encouraged to network and explore partnering opportunities.

Full conference passes include admission to all sessions and the exhibition as well as conference documentation.
Lunch, coffee breaks and the drinks reception provide ample time for networking and to continue discussions from the question and answer sessions.

http://www.selectbiosciences.com/conferences/DDLA2009

Agenda

Day One – 26 February 2009

Screening