The Symposium is sponsored by the European Federation of Medicinal Chemistry (EFMC).
The Organising and Scientific Committees cordially invite you to attend the 27 edition of this meeting on Trends in Drug Research. The interplay between molecular structure and biological activity is central to contemporary biomedical and translational research, relevant not only to structural biologists but also to diverse scientists involved in the study of bioactive compounds and signalling mediators and those working in drug discovery and development.
The scientific programme will include plenary lectures, oral communications and poster sessions. Registration will open on Sunday May 3, followed by an inaugural evening lecture and a welcome gathering.
The scientific programme ends on Thursday May 7 and the meeting will be concluded by the symposium dinner on Thursday evening. On Friday after the conference, a complimentary workshop “Virtual Screening and De Novo Design” is offered by BioSolveIT.
REGISTRATION Information and the complete SCIENTIFIC PROGRAMME is available on the SYMPOSIUM’S WEBSITE: WWW.NOORDWIJKERHOUTMEDCHEM.ORG
PROGRAMME
Opening keynote lecture
Chairman Prof. Henk TIMMERMAN (VU UNIVERSITY AMSTERDAM, Amsterdam, The Netherlands)
Chemistry’s Role In Target Identification And Validation Dr. Scott A. BILLER (NOVARTIS, Cambridge, United States)
KINASE INHIBITORS: TARGETING THE NON-ATP SITE
Chairman: Dr. Edmond DIFFERDING (UCB, Braine-l’Alleud, Belgium)
Discovery And Development of Selective, Orally Bioavailable Tyrosine Kinase Inhibitors For Targeted Treatment Of Human Cancers Prof. Stephen K. BURLEY (SGX PHARMACEUTICALS, SAN DIEGO, United States)
Non-Competitive Inhibitors of MEK1: from Discovery to the Clinic Dr. Jeffrey OHREN (PFIZER, GROTON, United States)
Allosteric Inhibition of Kinase Function Philip E. SANDERSON (MERCK, Rahway, United States)
CHEMICAL AND ENZYMATIC MODIFICATION OF THERAPEUTIC PEPTIDES AND PROTEINS TO IMPROVE THEIR MODE OF ACTION
Chairman: Dr. Stan VAN BOECKEL (ORGANON, Oss, The Netherlands)
Title to be announced
Dr. Jesper LAU (NOVO NORDISK, Maaloev, Denmark)
Sugars and Proteins
Prof. Ben DAVIS (OXFORD UNIVERSITY, Oxford, United Kingdom)
CarboCarrier(TM): a Novel Technology to Extend the Half-life of Small Proteins and Peptides Martin DE KORT (ORGANON, Oss, The Netherlands)
PROMISES IN GPCR DRUG DISCOVERY
Chairman: Prof. ROB LEURS (LEIDEN/AMSTERDAM CENTER FOR DRUG RESEARCH, Amsterdam, The Netherlands)
Structural Genomics of GPCRs; New Opportunities for Drug Discovery Chris TATE (MRC LABORATORY OF MOLECULAR BIOLOGY, Cambridge , Belgium)
GPCR Hetero-Dimerisation: Contribution to Receptor Pharmacology and Function Prof. Graeme MILLIGAN (UNIVERSITY OF GLASGOW, Glasgow, United Kingdom)
Dicovery & Development of Allosteric Modulators: Hopes and Promises Dr Emmanuel LE POUL (ADDEX PHARMA, Plan les Ouates, Switzerland)
TRANSPORTERS
Chairman: Prof. Gerhard ECKER (UNIVERSITY OF VIENNA, Vienna, Austria)
Predicting Substrate Properties for ABC-Transporter - Safety Sciences on the Molecular Level Prof. Gerhard ECKER (UNIVERSITY OF VIENNA, Vienna, Austria)
Drug Transport and Metabolism: Value of Knockout and Transgenic Mouse Models Dr. Alfred SCHINKEL (HET NEDERLANDS KANKER INSTITUUT , Amsterdam, The Netherlands)
Title to be announced
Prof. Robert FORD (THE UNIVERSITY OF MANCHESTER, Manchester, United Kingdom)
OFF-TARGET EFFECTS
Chairman: Prof. Hugo KUBINYI (Weisenheim am Sand, Germany)
GPCR Antitargets – Prediction and Prevention of Side Effects Dr. Thomas KLABUNDE (SANOFI-AVENTIS DEUTSCHLAND GMBH, Frankfurt am Main, Germany)
Understanding Ion Channels Using Computational Approaches Dr. Marcel J. DE GROOT (PFIZER, Sandwich, United Kingdom)
The QSARome of the Receptorome: Development of Robust QSAR Models Capable of Predicting Compound Binding Profiles against Multiple Targets Prof. Alexander TROPSHA (UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL, Chapel Hill, United States)
FRAGMENT BASED DRUG DISCOVERY
Chairman: Dr. Iwan DE ESCH (VRIJE UNIVERSITEIT AMSTERDAM, Amsterdam, The Netherlands)
Experiences in Fragment-based Lead Discovery Prof. Roderick E. HUBBARD (UNIVERSITY OF YORK, York, United Kingdom)
SPR Biosensor-Based Fragment Screening and Lead Characterization Prof. U. Helena DANIELSON (UPPSALA UNIVERSITY, Uppsala, Sweden)
Novel-Generation Kinase Inhibitors: Deep Pocket Binders by Fragment- Based Design Dr. Gerhard MÜLLER (CSO PROTEROS FRAGMENTS GMBH, Munich/Martinsried, Germany)
ANTI-INFLAMMATORY DRUG DISCOVERY
Chairman: Robin THURMOND (JOHNSON & JOHNSON, San Diego, United States)
Histamine H4 Antagonists as Future Anti-Inflammatory Drugs Robin THURMOND (JOHNSON & JOHNSON, San Diego, United States)
JAK3 Kinase: a Molecular Target for Treatment of Inflammatory Diseases and Renal Transplant Rejection Dr. Paul S. CHANGELIAN (CHANGELIAN BIOSCIENCE, LLC, , United States)
Molecular Mechanim of Action for Chemokine and Other Anti-inflammatory Agents on 7TM Receptors Dr. Thue W. SCHWARTZ (UNIVERSITY OF COPENHAGEN, Copenhagen, Denmark)
Complimentary Workshop on Friday: “Virtual Screening and De Novo Design” offered by BioSolveIT Late Departure - the transportation will be provided by the organisers.
Munich (D) and Leiden (NL), November 24, 2008 / b3c newswire / – CRELUX and ZoBio announced today that they have successfully executed their first fragment based screening projects from a jointly established platform.
One of the first targets, which also will be made accessible to customers, was Pim1, a kinase that has been implicated in the progression of several haematological malignancies. In addition to the “off the shelf” data on Pim1, tailor made fragment based screening projects are available for customers upon request.
The joint technology platform combines ZoBio’s proprietary Target Immobilized NMR Screening (TINS) technology with CRELUX’s high performance kinase crystallography platform. In the first campaign Pim1 was screened by TINS using ZoBio’s fragment library, hits were assessed in an in vitro kinase assay and the top 50 hits have been soaked into protein crystals. 37 out of these 50 fragments showed defined binding modes. Together with this high hit rate the structural diversity within this group generated multiple points for optimization and clearly proved the power of this technology combination.
“We are delighted to have found a perfect partner for entering into high performance fragment based screening. The collaboration with ZoBio adds another crucial drug discovery technology to our service portfolio”, commented Dr. Michael Schäffer, CEO of CRELUX.
“This project demonstrates the power of the combination of TINS with top notch crystallography. I am absolutely convinced that together we can provide our customers with critical starting point to jump start their challenging or failed targets.” noted Dr. Gregg Siegal, CSO of ZoBio.
CRELUX has used its state-of-the-art structural biology platform to solve more than 270 crystal and co-crystal structures for pharma and biotech companies. This platform encompasses all steps – from target cloning and expression all the way to high-throughput protein crystallization and in-house x-ray crystallography.
ZoBio provides fragment discovery and characterization services to the pharmaceutical and biotech industries using its proprietary Target Immobilized NMR Screening (TINS) platform. TINS, with its unparalleled sensitivity and reliability, has been used to discovery highly diverse, efficient ligands for a variety of targets including kinases, protein-protein interactions, viral targets and membrane proteins.
Jaidev had joined a leading Pharmaceutical Research Institute in India, for his Ph.D work. He reviewed his research plan thoroughly and also searched patents. Based on discussions with his guide, he formulated a very innovative research plan, pertaining to development of a new screening method for diabetic compounds. He started his work and after nearly 2 years of hard work, came up with very good data. He filed a patent in India and subsequently in the USA. He was confident of grant of patent, since nobody had done the work he had done.
The examination of his patent application started in the USA. He was shocked when his application in the USA was objected owing to a provisional patent filed by a researcher in USA. The provisional application filed by the USA researcher merely discussed theoritically an innovative research plan, very similar to the one proposed by Jaidev. However, there was no follow up after that and the researcher had abandoned the patent application. Mere theoritical discussion on the idea was there, without any data. However, it had been duly published and was in public domain. The US examiner objections were based on the observation, that Jaidev’s idea was not new- it had already been disclosed by someone else. Novelty was destroyed and Jaidev could not get a patent.
Discussion:
The case gives very important lessons for researchers:
1. Don’t wait for research work to be completed before filing a patent- even at initial stage or just when preliminary encouraging results give proof to an innovative concept, file a provisional patent application in India. It is quite cheap- govt. fee is just Rs.1000/- and in case you do it yourself, no further expense. But it protects your idea! After filing, within 12 months, you must file complete patent application, duly accompanied by data and including ‘claims’. In provisional, claims are not there.
2. Filing a provisional patent application can be done for a mere theoritical idea, with due discussion on the scientific and technical logic behind the concept. However, your filing date and hence PRIORITY gets protected from date of filing provisional.
Had Jaidev filed a provisionl application, well in time he might have been able to save his work. It was something very easy and simple, but because he was not aware, he waited to finish his work and lost the race to someone who was smart enough to file a provisional patent. However, the irony in this case is that even the US inventor did not get a patent, since he had not filed a complete patent application within one year. Maybe, he did not get success with experiments or some other problem. Jaidev did succeed in the Lab, but lost the patenting case, since his novelty had been destroyed by the US inventor.
Hence, do not underestimate the VALUE OF PATENTING YOUR IDEAS- THEY ARE PRECIOUS! FILE PROVISIONAL APPLICATIONS AT THE EARLIEST. DO NOT WAIT FOR YOUR RESEARCH TO FINISH.
Diagnosing and treating Cushing’s syndrome is sometimes just as difficult as it was 70 years ago.
For as long as it has been described, Cushing’s syndrome has presented physicians with a problem. Harvey Cushing first described it in 1932, and the diagnosis, differential diagnosis and treatment of Cushing’s have remained a major challenge for endocrinologists ever since.
Though uncommon, it is difficult to consider Cushing’s syndrome a rare occurrence. New research has shown Cushing’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.
“We are gaining an appreciation that Cushing’s is more common than it was once believed to be,” 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. “This fact points to the need for data regarding the value of the different diagnostic approaches and for data regarding treatment/outcomes in populations with Cushing’s.”
As most of the characteristics of Cushing’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 Cushing’s syndrome has become paramount.
The three most commonly performed diagnostic studies for Cushing’s syndrome — urine-free cortisol, low-dose dexamethasone suppression test and the nocturnal salivary cortisol — are also not without hurdles. All three have been shown to produce false positives and false negatives.
Approximately 80% of patients with Cushing’s syndrome have an adrenocorticotropic-secreting neoplasm from a pituitary tumor (Cushing’s disease) or a nonpituitary neoplasm, and the treatment of Cushing’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.
“Cushing’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,” 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. Cushing’s discovery, what are the best methods of diagnosis and treatment for Cushing’s syndrome? Endocrine Today talked with leading researchers in the field to uncover the current trends in Cushing’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 Cushing’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.
“The presence of Cushing’s syndrome should be considered if these medical conditions are present, though diagnostic testing should be performed only in subjects who have signs favoring Cushing’s, such as demonstration of objective proximal weakness, spontaneous ecchymoses and violaceous striae,” Katznelson said.
“For example, central obesity with supraclavicular and dorsicervical fat pads would favor a diagnosis of Cushing’s syndrome, in contrast to the presence of generalized obesity,” he said.
Raff and Findling noted in a recent clinical review that endogenous cortisol excess also leads to fairly specific catabolic effects — 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.
“There is no clear guideline,” said Roberto Salvatori, MD, associate professor of medicine in the division of endocrinology at Johns Hopkins University School of Medicine. “You need to keep your mind open.”
“Sometimes Cushing’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 Cushing’s. However, anytime a physician thinks about the possibility of a patient having the disease, work-up should be initiated,” he said.
Testing options
Opinions varied when Endocrine Today asked researchers which of the three tests for Cushing’s syndrome was most reliable.
“No test is 100% sensitive or specific,” Salvatori said. “I always use two, sometimes three, screening tests.” 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 Cushing’s syndrome do not have elevations of urine-free cortisol, “making it a poor screening test for this condition.”
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 Cushing’s syndrome that performs better than the late night/midnight salivary cortisol method. The concept is based on the fact that patients with mild Cushing’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.
“Because each of these tests has associated false positives and negatives, a combination of these tests is often necessary for a valid diagnosis,” Katznelson said. “In the end, these tests need to be considered in the context of a history and physical examination that favors this diagnosis.”
Lynette Nieman, MD, associate director of the Intramural Endocrinology Training Program at the NIH, agreed. “Of the three recommended tests, each is useful in certain conditions,” she said. “I 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.”
Ruppe said the choice between the tests should be based on patient characteristics that will allow for adequate collection of each sample. “For 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.”
Ruppe also noted that one possible improvement would be to improve standardization of the assays across different labs. “Since there is no standardization, the quality of the performance of the assay can vary across different facilities and centers,” 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 Cushing’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 Cushing’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.
“Some people would say that every patient should have it because it is the one best test for the differential diagnosis of ACTH-dependent Cushing’s syndrome,” Nieman said. “However, patients in whom data strongly suggest Cushing’s disease might forego it.”
“In 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,” Salvatori said. “But even the International Prostate Symptom Score is not 100% sensitive or specific.” 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 Cushing’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 Cushing’s disease is referral to a neurosurgeon with extensive experience.
“Referral to a neurosurgeon who is highly experienced in this procedure is critical,” 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.
“In Cushing’s disease, this is especially true,” Katznelson said. “Because 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,” Katznelson said.
“There is no doubt that the surgeon’s experience influences the success rate,” 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 Cushing’s syndrome prior to a referral to a neurosurgeon.
“There is nothing worse than an inexperienced surgeon operating on a patient with Cushing’s or a surgeon operating on a patient who does not have a firm diagnosis of Cushing’s syndrome,” Stratakis said.
“Surgery offers a reasonable chance for cure in the hands of an experienced neurosurgeon,” said Amir Hamrahian, MD, a staff physician at the Endocrinology Institute at the Cleveland Clinic. “We are currently involved in two studies looking at new medications for medical treatment of patients with Cushing’s syndrome. However, surgery is still the best initial approach for those not cured,” Hamrahian said.
The future
“Medications are the future for patients with inoperable, recurrent Cushing’s syndrome,” 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 Cushing’s disease. Raff said he believes that clinical trials in patients with Cushing’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
“Microsurgical improvements will also be significant, but the major problem right now is the number of patients who are left untreated with recurrent disease,” Stratakis said. “For 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,” 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 Cushing’s.
“Technical advances in surgery including endoscopic pituitary surgery and pseudocapsular dissection can improve surgical outcomes,” Liu said.
Katznelson said he hopes the future will bring improved diagnostic strategies important for detecting true Cushing’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.
“These studies will hopefully lead to novel medical options for this syndrome,” Katznelson said. “There 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.” – 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 Cushing’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 Cushing’s syndrome. Nat Clin Pract Endocrinol Metab. 2008;4:344-350.
* Findling JW, Raff H. Cushing’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 Cushing’s disease after unsuccessful transsphenoidal surgery. Neurosurg Focus. 2007;23:E8.
* Nieman L. The dexamethasone-suppresssed corticotropin-releasing hormone test for the diagnosis of Cushing’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 Cushing’s disease. Neurosurg Focus. 2007:23:E2.g
Today, Nanion announces the late-stage development of a new automated patch clamp platform: the SyncroPatch 96. Developed to meet the throughput demands of industrial ion channel drug screening and safety profiling, and with a price-per-data-point compatible with screening standards, the SyncroPatch 96 will offer the highest throughput in the market for high quality HTS-oriented ion channel screening.
Munich, Germany, November 20, 2008 –(PR.com)– Following the successful market introduction of two automated patch clamp devices, the Port-a-Patch (2004) and the Patchliner (2006), Nanion now introduces the SyncroPatch 96. Nanion’s Patchliner and Port-a-Patch platforms enjoy great popularity in both academic and industrial settings and have received enthusiastic user feedback in customer surveys such as the HTStec report. Building on their success, the new SyncroPatch 96 vastly increases throughput while reducing the cost per data point to a level compatible with industrial ion channel screening requirements.
“There is a gap between the demands in ion channel drug screening and the capability of the high quality automated patch clamp platforms currently available on the market. Pharmaceutical companies want higher throughput and lower cost per data point, whilst maintaining data quality. The SyncroPatch96 will fill this gap, by providing high throughput, high quality patch clamp recordings, at a low enough cost to keep screeners happy.” says Dr. Niels Fertig, CEO of Nanion.
The SyncroPatch 96 acquires simultaneous recordings from 96 individual cells in a well-plate format and allows for screening of both ligand- and voltage-gated ion channels. The platform supports giga-seal recordings, continuous recording during compound application and addition of multiple compounds to each of the 96 cells. The SyncroPatch 96 will be launched in 2009.
About Nanion:
Nanion Technologies GmbH is a German Private Limited Company and was founded in 2002 as a spin-off from the Center for Nanoscience (CeNS) of the University of Munich. Nanion’s team has developed and globally established two highly successful automated patch clamp instruments as enabling tools for sophisticated and high throughput applications for ion channel research and drug discovery.
Nanion’s instruments use planar patch clamp chips which replace the traditional glass pipette used in the technique of patch clamping. Nanion was nominated in 2007 for Germany’s most prestigious innovation award the Deutscher Zukunftspreis (German Future Prize, Federal President’s Award for Technology and Innovation).
ePT–the Electronic Newsletter of Pharmaceutical Technology
Company Notes
San Jose, CA (Nov. 14)—AnaSpec established a new facility dedicated to peptide production that complies with good manufacturing practice (GMP). The new facility is adjacent to AnaSpec’s headquarters and provides 5000 ft2 of dedicated GMP space, including two Class 10,000 cleanrooms. AnaSpec produces GMP peptides in milligram to kilogram quantities.
West Lafayette, IN (Nov. 12)—Bioanalytical Systems (BASi), a provider of contract laboratory services and manufacturer of scientific instruments, opened its new European laboratory and office in Warwickshire, United Kingdom. The new 10,000-ft2 facility offers bioanalytical capability and provides access to BASi’s preclinical and pharmaceutical analysis services. BASi Europe distributes BASi instruments and equipment and provides support for customers and distributors throughout Europe.
Rockville, MD (Nov.18)—BioReliance concluded an agreement with Provecs Medical (Hamburg, Germany) for the production of investigational quantities of “Immunalon,” a novel therapeutic agent based on an adenovirus vector that stimulates an immunological response against tumor cells.
Mechelen, Belgium (Nov. 18)—Galapagos concluded collaboration agreements with Merck Serono, a division of Merck KGaA (Darmstadt, Germany). The total value of the contracts for Galapagos is EUR 1.1 million over one year. Galapagos’s BioFocus DPI service division will provide “SoftFocus” compounds for Merck Serono’s drug-discovery programs. In a separate agreement, BioFocus DPI will perform medicinal-chemistry services on an undisclosed Merck Serono program. The latter agreement is an extension of a long-running collaboration that was last expanded in 2005.
Cambridge, MA (Nov. 17)—Genzyme and the International Center for Genetic Engineering and Biotechnology (ICGEB, Trieste, Italy), a not-for-profit research and development organization, will collaborate to advance treatments for neglected diseases. The research agreement between Genzyme and ICGEB will initially focus on the development of new treatments for malaria. The research will take place in ICGEB’s laboratories in New Dehli, India, and in Genzyme’s facilities in Waltham, Massachusetts. Scientists from Genzyme and ICGEB will sometimes work in each other’s laboratories.
Toronto, Ontario, Canada (Nov. 14)—Patheon and Solvias (Basel) formed a global alliance to offer integrated development services to pharmaceutical and biotechnology companies. This alliance combines Patheon’s formulation-development experience with Solvias’s preformulation and solid-state chemistry capabilities. The companies will provide early-development services such as active-ingredient characterization, salt selection and cocrystallization, polymorphism screening, solubility determination, excipient compatibility, and formulation.
Fairfax, VA (Nov. 17)—SRA International, a provider of technology and strategic consulting services and solutions to government organizations and commercial clients, won a contract with the Centers for Disease Control and Prevention (CDC) to provide laboratory support services to the Select Agent Program. Under the contract, SRA will continue to help CDC track the possession, use, and transfer of select agents (biological agents and toxins that could potentially threaten public health and safety if released into the environment) in the US. The company’s work includes certifying that proper biosafety and biosecurity measures are in place in laboratories, processing select agent-transfer requests, and tracking all shipments of select agents between registered facilities.
Menlo Park, CA (Nov. 18)—SRI International, an independent, nonprofit research and development organization, was awarded a $1,788,011 contract by the National Institute on Drug Abuse (NIDA). The award is a continuation of two previous NIDA contracts for which SRI has provided chemical analysis of synthetic peptides and related compounds, as well as drugs of abuse. Under the contract, SRI researchers will provide NIDA with purity, stability, and authenticity analysis of synthetic peptides and compounds in NIDA’s medications-development program.
People Notes
Watertown, MA (Nov. 17)—Howard Bernstein resigned from his position as Acusphere’s executive vice-president of research and development to pursue new opportunities. During Bernstein’s 14-year career with the company, he led the development of its lead product candidate, which is currently awaiting approval by the US Food and Drug Administration. Bernstein also was instrumental in the development of Acusphere’s core microsphere technology platform and in devising ways to apply that technology to potential new and existing drugs.
Cambridge, MA (Nov. 17)—Ascent Therapeutics completed its senior management team by appointing Frederick Jones president and chief executive officer and Stephen Hunt senior vice-president of discovery research. Ascent is an emerging biopharmaceutical company developing “Pepducin” lipopeptides, a novel class of G protein-coupled receptor modulators to treat serious illnesses.
Wilmington, DE (Nov. 18)—AstraZeneca appointed Rich Fante president of the company’s US business. Fante succeeds Tony Zook, whose role was expanded when he was named president of MedImmune (Gaithersburg, MD), AstraZeneca’s wholly owned biologics business. Fante previously served as AstraZeneca’s vice-president of brand strategy and portfolio operations. He led the development and execution of marketing strategies for all AstraZeneca brands in the US.
West Lafatyette, IN (Nov. 14)— Anthony S. Chilton is joining Bioanalytical Systems (BASi) as chief operating officer of scientific services, effective Dec. 1, 2008. Chilton will have responsibility for the scientific services provided to BASi’s customers from three locations in the US and one in the UK.
Houston, TX (Nov. 18)—CytoGenix’s board of directors appointed Lex M. Cowsert to the positions of president, chief executive officer (CEO), and director, effective immediately. Randy Moseley, who was serving as interim CEO, resigned from this position but will remain chairman of CytoGenix’s board and principal financial officer.
KINGSTON, England, Nov. 25, 2008-Guava Technologies, Inc. presented at the recent Molecular Targets & Cancer Therapeutics Symposium* information on their recent advancements that describe an experimental methodology and the new Guava® Simplicity Analysis Software which exploit the advantages of plate based flow technology. These technological improvements result in an overall process that can significantly expedite the drug discovery process by providing a means for extraction of key findings from the highly complex data sets encountered with functional screening of siRNA knockdown assays.
Solid tumors comprise genetically heterogeneous cell populations whose growth and survival depends on the complex interplay of distinct, yet overlapping, signaling networks. A major challenge in developing a course of therapy is determining which signaling nodes to target for a specific malignancy. Profiles from siRNA gene silencing are integral to mapping disease-specific signaling cascade(s) and provide insight to key targets for therapeutic intervention. Successful siRNA screening relies not solely upon optimizing transfection, but also cell analysis systems capable of high content screening (HCS) at the single cell level, within overall populations (sample well), and across multiple data sets.
The presentation describes how the Guava EasyCyte™ Plus System, with integrated Guava Simplicity Software, provides a revolutionary platform for secondary target validation and compound screening. Guava Technologies’ flow cytometers overcome the limitations of inference-based measurements of transfection efficiency and protein knockdown through direct quantitiative analysis of populations at the single cell level. The Simplicity Analysis Software’s intuitive architecture and ease of use facilitates the process of asking biological questions on multi-dimensional data sets through visualisation of user-defined parameters in the form of heat-maps. Most importantly, comparative results are displayed at the experiment level rather than on an individual well/sample basis.
Specifically, using the EasyCyte Plus System in tandem with Simplicity Analysis Software, 23 agents were identified that had growth restrictive properties although significant variation across cell lines was observed. Further targeted gene knockdown via siRNA confirmed the presence of both activators and inhibitors of Camptothecin-induced apoptosis as well as gene targets for growth arrest. Screens for apoptosis and cell cycle, as well as phospho-signaling intermediates, defined compounds with mechanisms of action similar to and different from Camptothecin. Cell-based assays for phenotype and function revealed a number of cooperative and antagonistic interactions between signaling intermediates, their respective cascades, and cytoactive agents.
Overall, the acquired multiplex data set is shown to provide a more detailed view on the behaviour of each of the test compounds with respect to apoptotic induction, cell cycle progression, and the signaling cascades that regulate these cellular responses to drug treatment. In total, this experimental methodology, when used in conjunction with Guava Technologies’ cell analysis platforms and Simplicity Analysis Software, significantly expedites the drug discovery process by providing a means for extraction of key biological findings from complex result sets.
If you would like more information on this application it is available for download from http://guavatechnologies.com/cm/Resources/Scientific%20Pubs.html. More information about the company and its products is available at www.guavatechnologies.com.
Guava Technologies, Inc., a privately held biotechnology company, is the leading provider of on-demand, easy-to-use single cell analysis systems. Guava® Systems, including the Guava® Personal Cell Analysis (PCA), Guava Auto CD4/CD4%, Guava® PCA-96 and Guava EasyCyte™ Systems, are integrated, fully optimised, microcapillary cytometry systems with embedded absolute cell counting capability. Used worldwide by the life sciences, biotechnology, and pharmaceutical industries, as well as clinical testing institutions (outside the United States and Europe), products from Guava Technologies have broad applications in scientific research and throughout the drug discovery and lead optimisation process, as well as for cell counting and optimisation of commercial biopharmaceutical production. Guava Technologies offers a variety of assays and dedicated software modules for the Guava Systems, enhancing the system’s overall ease-of-use.
* Guava, Guava Technologies Logo, and all other trademarks are property of Guava Technologies, Inc. * Guava® Simplicity Analysis Software is for Research Use Only. Not for use in Diagnostic procedures. * This symposium took place at the EORTC-NCI-AACR meeting in Geneva, Switzerland (21-24 October 2008)
Munich, Germany, November 18th, 2008; Today, Nanion announces the late-stage
development of a new automated patch clamp platform: the SyncroPatch 96.
Developed to meet the throughput demands of industrial ion channel drug screening
and safety profiling, and with a price-per-data-point compatible with screening
standards, the SyncroPatch 96 will offer the highest throughput in the market for high quality HTS-oriented ion channel screening.
Following the successful market introduction of two automated patch clamp devices, the Port-a-Patch (2004) and the Patchliner (2006), Nanion now introduces the SyncroPatch 96. Nanion’s Patchliner and Port-a-Patch platforms enjoy great popularity in both academic and industrial settings and have received enthusiastic user feedback in customer surveys such as the HTStec report. Building on their success, the new SyncroPatch 96 vastly increases throughput while reducing the cost per data point to a level compatible with industrial ion channel screening requirements.
“There is a gap between the demands in ion channel drug screening and the capability of the high quality automated patch clamp platforms currently available on the market. Pharmaceutical companies want higher throughput and lower cost per data point, whilst maintaining data quality. The SyncroPatch96 will fill this gap, by providing high throughput, high quality patch clamp recordings, at a low enough cost to keep screeners happy.” says Dr. Niels Fertig, CEO of Nanion.
The SyncroPatch 96 acquires simultaneous recordings from 96 individual cells in a well-plate format and allows for screening of both ligand- and voltage-gated ion channels. The platform supports giga-seal recordings, continuous recording during compound application and addition of multiple compounds to each of the 96 cells. The SyncroPatch 96 will be launched in 2009.
About Nanion:
Nanion Technologies GmbH is a German Private Limited Company and was founded in 2002 as a spinoff from the Center for Nanoscience (CeNS) of the University of Munich. Nanion’s team has developed and globally established two highly successful automated patch clamp instruments as enabling tools for sophisticated and high throughput applications for ion channel research and drug discovery.
Nanion’s instruments use planar patch clamp chips which replace the traditional glass pipette used in the technique of patch clamping. Nanion was nominated in 2007 for Germany’s most prestigious innovation award the Deutscher Zukunftspreis (German Future Prize, Federal President’s Award for Technology and Innovation).
Zurich, Switzerland; Carlsbad, USA; Vienna, Austria, November 20, 2008 – At the closing of BIO-Europe 2008 in Mannheim/Heidelberg which saw 2400 life science executives engage in an astounding 10,250 one-to-one meetings, EBD Group today announced that next year’s BIO-Europe partnering conference will pay a visit to Vienna, Austria. The 15th annual edition of BIO-Europe, the world’s largest stand-alone partnering event will gather leaders of the life science industry at the Wiener Messe on Nov. 2–4, 2009 to take dealmaking to a new level. This represents the first time in the conference’s 14 year history that it will venture outside of Germany, and is testimony to the recognition of the Vienna region’s emergence as a robust cluster of biotech innovation.
Joining LISA VR in welcoming BIO-Europe 2009 will be the Ministry for Economic Affairs and Labor, the City of Vienna, the Austrian Business Agency and the Center for Innovation and Technology. In the recent years over 140 life science companies have been established in Vienna.
“The biotechnology scene in our region already employs nearly 10,000 people many of whom specialize in red biotechnology. Five life science universities, outstanding research institutions such as IMP and IMBA, international corporations with headquarters in Vienna for the Eastern and South Eastern European markets and numerous dynamic start-up companies have combined to make the industry a showpiece for Austrian technology policy,” said Michaela Fritz and Eva Czernohorszky, Managing Directors of LISA VR.
Latest news from the Viennese emerging start-up scene offer proof of the dynamism of this young life science location. For example, Affiris recently secured EUR 430 million from GlaxoSmithKline for the rights to its Alzheimer’s vaccines currently under development, emerging company Intercell is close to market with its Japanese Encephalitis Vaccine, and Fibrex is a company worth monitoring after its positive Phase II results for FX06, a fibrin derived peptide for the treatment of reperfusion injury in myocardial infarction.
Vienna is home to the Research Institute for Molecular Pathology, the Institute of Molecular Biotechnology, the Austrian Center of Biopharmaceutical Technology, the Austrian Breast and Colorectal Cancer Study Group and the Gregor Mendel Institute for Molecular Plant Biology.
The University of Vienna, the Medical University of Vienna, the University of Natural Resources and Applied Life Sciences, the University of Veterinary Medicine and the Vienna University of Technology represent five of the universities with a focus on life sciences located in the capital.
Global life science players in Vienna include Baxter BioScience, Boehringer Ingelheim Austria, Eli Lilly’s Vienna School for Clinical Research, Sanochemia and Octapharma.
About EBD Group
EBD Group is the leading partnering firm for the global life science industry. Since 1993, biotech, pharma and medical device companies have leveraged EBD Group’s partnering conferences, technology and services to identify business opportunities and develop strategic relationships essential to their success.
EBD Group’s conferences are run with the support of leading corporations and international trade associations and include:
• BIO-Europe and BIO-Europe Spring(R), the world’s largest stand-alone life science partnering conferences, supported by the Biotechnology Industry Organization (BIO)
• BioPharm America(TM), EBD Group’s North American partnering event
• EuroMedtech(TM), EBD Group’s new partnering event for the innovative medical technology industry
• BioEquity Europe, the investor conference co-organized with BioCentury Publications and BIO
EBD Group’s sophisticated Web-based partnering service, partneringONE(TM), is used as the partnering engine at numerous third-party events around the world. Outside of the conference format, EBD Group’s consultants provide hands-on assistance for firms seeking to in- or out-license products and technologies.
EBD Group has offices in the USA and Europe.
For more information please visit www.ebdgroup.com
About BIO
BIO represents more than 1,200 biotechnology companies, academic institutions, state biotechnology centers and related organizations across the United States and in more than 30 other nations. BIO members are involved in the research and development of innovative healthcare, agricultural, industrial and environmental biotechnology products. BIO also produces the BIO International Convention, the world’s largest gathering of the biotechnology industry, along with industry-leading investor and partnering meetings held around the world.
Mechelen, Belgium; 18 November 2008 – Galapagos NV (Euronext: GLPG) announced today new collaboration agreements with Merck Serono, a division of Merck KGaA, Darmstadt, Germany. Total value of the contracts for Galapagos is €1.1 million over one year.
“BioFocus DPI has a long relationship with Merck Serono in medicinal chemistry, which we are pleased to extend again this year,” said Onno van de Stolpe, CEO of Galapagos. “The purchase of BioFocus DPI’s SoftFocus libraries underscores our ability to grow business with clients.”
About Galapagos and BioFocus DPI
Galapagos (Euronext Brussels: GLPG; Euronext Amsterdam: GLPGA; OTC: GLPYY) is a drug discovery company with pre-clinical programs in bone and joint diseases and bone metastasis. Its BioFocus DPI division offers a full suite of target-to-drug discovery products and services to pharmaceutical and biotech companies, encompassing target discovery and validation, screening and drug discovery through to delivery of pre-clinical candidates. BioFocus DPI also provides adenoviral reagents for rapid identification and validation of novel drug targets, compound libraries for drug screening as well as ADMET database products to select compounds. Galapagos currently employs about 460 people and operates facilities in six countries, with global headquarters in Mechelen, Belgium. More information about Galapagos and BioFocus DPI can be found at www.glpg.com and www.biofocusdpi.com.
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