Bio Screening Industry News

Services to accelerate programs from biological target to first-in-man use Idealp-Pharma is launching fully integrated drug discovery and preclinical development services combining medicinal chemistry, cheminformatics,
screening, early ADMET and preclinical development capabilities to speed up
partner’s and client’s small molecules programs from biological target to firstin-
man use.

According to Serge Petit, PhD, President and CEO, “Being a one-stop-shop company adds significant value because the lead optimisation process involves iterative cycles for incremental optimization. The main advantages of our one-stop-shop service are to have access to all the experimental data, to be able to refocus the synthesis program and then to make the best decision for the lead optimisation process in accordance with our customers’ specifications.”

“Idealp-Pharma manages its customers’ hit discovery and validation, hit-to-lead
progression and lead-to-candidate process. Our aim is to deliver chemically and
biologically validated hits, accelerating lead optimization and identying IND candidate for our customers”, said Serge Petit. Idealp-Pharma supports also its client’s drug discovery activities by providing modular and customized services such as medicinal chemistry and cheminformatics studies.

More information about integrated drug discovery services can be found at www.idealp-pharma.com
About Idealp-Pharma

Idealp-Pharma’s aim is to expand partner’s drug pipeline by accelerating drug
discovery process from the biological target to first-in-man use. Idealp-Pharma
provides a range of flexible services: including fully integrated drug discovery and preclinical development, medicinal chemistry and cheminformatics.

Idealp-Pharma’s purpose-built lab covers a total of 2000 square meters. Idealp-Pharma now employs 60 staff. More information about Idealp-Pharma can be found at www.idealp-pharma.com

Genedata and Axxam have signed a multi-year contract for the implementation of the Genedata Screener® data analysis and management platform into Axxam’s high throughput screening process.

Genedata, the leading provider of in silico solutions for the pharmaceutical and life science industries, and Axxam, a leading biotechnology research organization offering early-stage discovery research services for the life science industry, have signed a multi-year contract for the implementation of the Genedata Screener® data analysis and management platform into Axxam’s high throughput screening process.

With an increasing number of pharma and life science companies outsourcing entire stages of their research cycle, the contributions of contract research organizations (CROs) to drug development have never been more crucial. Faster development, earlier decisions on project failures, and higher approval success rates are becoming the norm. To continuously meet those high standards, Axxam relies on Genedata Screener. Screener’s high-quality, high-performance modular system rapidly and flexibly analyzes, integrates and manages all assay data and then combines it with chemical, pharmacological and in vivo information to support Axxam scientists in prioritizing compounds and identifying quality lead structures with the highest confidence. Screener`s open and scalable architecture integrates with existing infrastructures, which allows it to be tailored to specific discovery processes, maximizing value.

Dr. Stefan Lohmer, CEO of Axxam, said, ”Establishing flexible and efficient working practices to ensure client satisfaction is our top priority as a reputable service provider. Genedata’s consistently high performance and data quality along with their expertise and profound scientific knowledge enable us to meet that goal on a daily basis, with rigorous quality control covering every detail, as well as keeping to deadlines and budget terms. Thus, our focus extends beyond the actual license agreement with Genedata, towards a comprehensive, long-term partnership in high throughput screening.”

Dr. Othmar Pfannes, CEO of Genedata, stated, “We are proud to have met Axxam’s high selection standards. Genedata as leading research informatics provider and Axxam as ‘best-in-class’ contract research organization for life science discovery research are creating a powerful synergy here that lets us look with excitement to the future.“

Axxam is a science-driven biotechnology company, which offers early-stage discovery research services for the life science industry. The company applies its comprehensive from genes to leads activities to Discovery Services that we provide for customers and to internal Discovery Research. Activities include assay development, high-throughput screening (HTS) and compound profiling. A team of almost 70 qualified personnel is committed to advance the discovery projects of our partners. The scientific know-how of our team is built upon years of experience as part of the assay development group of the Bayer HealthCare, Research and Development organization prior to the late 2001 inauguration of Axxam as an independent private company. The growing list of our collaborations in the life science industry is recognition of our success in areas such as the pharmaceutical, agrichemical, fragrance, cosmetic, flavour, food and beverage branches. Axxam is a privately-owned company with offices and state-of-the-art laboratories located in the San Raffaele Biomedical Science Park, Milan.

Genedata specializes in discovery informatics for biotech, pharmaceuticals and the life sciences. The company offers expertise in research informatics combined with open and scalable computational solutions. Our product suites include Genedata Phylosopher® for integrating, structuring, and analyzing research data, Genedata Screener® for high throughput screening, high content screening analysis and hit-to-lead, and Genedata Expressionist® for omics data integration, processing and analysis. Founded in 1997 as a privately held spin-off from Novartis, Genedata is headquartered in Basel, Switzerland, and has branches in Munich (Germany), Konstanz (Germany), Boston (USA), San Francisco (USA), and Tokyo (Japan). The company is also represented in Taiwan and Singapore.

From Focused Compound Libraries to optimised Hit-to-Lead - that’s the motto of IQPC’s 4th international conference on “Compound Libraries” (formerly “Focused Compound Libraries”). Nowadays the pharmaceutical industry is under enormous pressure, and the key for the industry to survive is faster and more efficient drug discovery. To improve their lead generation process and library, pharmaceutical companies need to choose the correct library design from the very beginning. Also, they need to integrate new compounds and collections into their library design to guarantee its continuous improvement. However, urgent questions still remain: How can you find the ideal library size to assure diversity while keeping focused? Can fragment based screening speed up the discovery process? How can you guarantee the best screening outcome analysis to ensure lead optimization?

After concentrating on focused compound libraries in the past years, this year presentations will cover the design and enhancement of different kinds of libraries as well as the possibilities of hit-to-lead optimization.

Maximize your knowledge of the latest advances in intelligent library design:

• Explore how to efficiently integrate new compounds and collections to improve the lead generation process
• Learn how to build up an effective collection of compounds in your company to guarantee physical quality and quantity of the compounds
• Hear about enhanced screening methods such as fragment-based screening to reduce complexity in the screens
• Successfully enlarge your compound collection by utilising novel structures and multi-component reactions in library design
• Enhance your Hit-to-Lead ratio through advances in library design, screening methods and structure based drug discovery approaches

Experts from international companies such as Pfizer, AstraZeneca, Merck, Grünenthal, Sanofi-Aventis and many more will report about first-hand experiences and best practices.

Full speaker line-up:

• Sanofi-Aventis Gruppe, Germany
• AstraZeneca Ltd., UK
• Merck Serono, Germany
• Basilea Pharmaceutica International AG, Switzerland
• Organon Laboratories Ltd., UK
• GenKyotex S.A., Switzerland
• Carlsberg Laboratory, Denmark
• Chemical Genomics Centre of the Max-Planck-Society, Germany
• AstraZeneca, R&D Mölndal, Sweden
• AnalytiCon Discovery GmbH, Germany
• Asinex Ltd., Russia
• TU Vienna, Austria
• BioFocus DPI Limited, UK
• Solvay Pharmaceuticals BV, Netherlands
• Grünenthal GmbH, Germany
• Novartis, Switzerland
• Bayer CropScience AG, Germany
• Pfizer Ltd., UK

http://www.iqpc.com/ShowEvent.aspx?id=113724

Present advances in screening and separation technologies reveal extracts bioactivity with great efficiency and accuracy. Recently reported method of Direct Screening of Natural Products Extracts Using Mass Spectrometry does not require any preparation or fractionation work. Several hundred crude extracts can be screened per one day. Direct bioaffinity screening mass spectrometry method followed by the use of ligand mass information for mass-directed purification makes screen of crude extracts and identification of active compounds precisely possible.

Vu, H., et. al. Direct Screening of Natural Product Extracts Using Mass Spectrometry. J. of Biomol. Screening. 2008, v. 13, 4, 265-275

Plants and plant extracts from Timtec

HAMBURG, Germany and OXFORD, England and OSLO, March 12, 2008 /PRNewswire-FirstCall/ — Evotec AG announced today that Spermatech A/S has chosen them as a partner to identify small molecule therapeutics for their pharmaceutical discovery project.

Through the study of the physiology of sperm motility, more specifically of “rapid swimmers” that cause fertilisation, Spermatech have identified biological targets that could be exploited in the development of non-hormonal reversible male contraceptives. On this basis, Evotec and Spermatech have defined a strategy for a tailored drug discovery project. Evotec will apply its expertise and proprietary technologies in assay development, high throughput screening and NMR (Nuclear Magnetic Resonance) screening to identify inhibitors of the sperm specific target protein. The screening will be performed with Evotec’s screening library of 250,000 drug-like compounds. Compounds will be identified that reduce sperm motility and will be used in the development of non-hormonal reversible male contraceptives at Spermatech. In addition, compounds that promote target activity may be evaluated as supporters of male fertility.

Dr Mark Ashton, Executive Vice President Business Development Services at Evotec, said: “We are extremely pleased that Spermatech has selected Evotec for this interesting project. It will allow us to use our combined technologies in assay development, high-throughput screening and NMR screening to identify the most promising candidates in the therapeutic field. Evotec’s highly diverse compound library is a good starting point to identify such active molecules and the additional results from NMR investigations of the hits with the target protein will provide the medicinal chemists with useful information to support subsequent drug design.”

“We were impressed by Evotec’s highly specialized and integrated capabilities. The collaboration will provide us with access to state-of-the-art assay development and screening technology and expertise together with a high quality library of small molecules. We are confident that this will provide an excellent starting point and valuable information to progress the molecules into more advanced stages. We really appreciated that during the initial scientific discussions of the project Evotec clearly demonstrated a results-oriented spirit in support of our project.” commented Eirik Naess-Ulseth, Chief Executive Officer, Spermatech.

Forward looking statements

Information set forth in this report contains forward-looking statements, which involve a number of risks and uncertainties. Such forward-looking statements include, but are not limited to, statements about the anticipated benefits of Evotec’s products and services, the payments that Evotec may receive under its collaboration agreement with Spermatech, the anticipated timing and results of Evotec’s clinical and pre-clinical programs, and other statements that are not historical facts. Evotec cautions readers that any forward-looking information is not a guarantee of future performance and that actual results could differ materially from those contained in the forward-looking information as a result of risks and uncertainties. These include risks and uncertainties relating to: Evotec’s ability to complete the merger because conditions to the closing of the merger may not be satisfied; the failure to successfully integrate the businesses of Evotec and Renovis; unexpected costs or liabilities resulting from the merger; the risk that synergies from the merger may not be fully realized or may take longer to realize than expected; disruption from the merger making it more difficult to maintain relationships with customers, employees or suppliers; competition and its effect on pricing, spending, third-party relationships and revenues; the need to develop new products and adapt to significant technological change; implementation of strategies for improving internal growth; development, use and protection of intellectual property; general worldwide economic conditions and related uncertainties; future legislative, regulatory, or tax changes as well as other economic, business and/or competitive factors; and the effect of exchange rate fluctuations on international operations.

The risks included above are not exhaustive. The Registration Statement on Form F-4 filed by Evotec with the Securities and Exchange Commission contains additional factors that could impact the combined company’s businesses and financial performance. The parties expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in the parties’ expectations or any change in events, conditions or circumstances on which any such statement is based.

Federal scientists are collaborating on a new approach to testing the toxicity of chemicals ranging from pesticides to household cleaners. They plan to use new automated high-speed cell tests to get more reliable data faster and more cheaply, and with less reliance on animal testing.

The National Institutes of Health and the U.S. Environmental Protection Agency are partners in the plan. NIH director Elias Zerhouni says scientists will apply technology developed by the two agencies to identify chemicals that might be harmful to humans.

“You could, in a battery of tests, end up with very specific molecular signatures that will be predictive of human toxicology, in ways that you just can’t do in animal testing today,” he said.

Scientists now rely heavily on animal tests to generate chemical toxicity data. That process is expensive, time-consuming and not always the best predictor of effects on humans says Francis Collins, director of the NIH National Human Genome Research Institute.

“There are differences between species. We are not rats and we are not even other primates, and so that [the] desire here is to see if we could do better,” she said. “Ultimately what you are looking for is [whether] this compound does damage to cells.”

The high-speed automated screening looks at the effects of chemical compounds on single human cells rather than on an entire laboratory animal. Researchers expect the new toxicology testing method will expand the number of chemicals tested and reduce the time, money and use of animals. NIH director Elias Zerhouni says it will also generate data more relevant to humans.

“What is being proposed here is to move the 20th century paradigm of testing of one compound at a time in many animals to going to the 21st Century paradigm [that] tests 5,000 to 10,000 compounds against 20,000 conditions in cells that are very specific to human toxicology,” he said.

Since NIH started the National Toxicology Program 30 years ago, it has tested 2,500 chemicals. Using the new automated strategy could get the same job done in a single afternoon.

John Butcher, associate director of the National Toxicology Program, explains that to check the reliability of this approach, scientists will first do a comparative analysis of the 2,500 chemicals previously tested on animals.

“And we can compare the output from these cell-based assays, in terms of whether these chemicals cause cancer, reproductive and developmental effects, neurological effects, immunotoxic effects and various other kinds of toxicity,” he said.

Butcher says the anticipated shift away from animal testing could take many years. Writing in Science Magazine, he says the agencies expect broader participation from public and private partners in the scientific community as the cell-based testing methods are refined and accepted.

SAN JOSE, Calif.--(Business Wire)--HTS laboratories continue to evolve their processes and strategies
to increase their success rates and improve efficiencies in their drug
discovery efforts. New strategies include the use of phenotypic and
pathway-based assays in primary or secondary screening, the use of new
targets and the expansion in the diversity of compounds screened for
new drug candidate leads. The Directors at HTS laboratories also plan
to employ new technologies, including the use of label-free
technologies and new detection systems to aid in finding new drug
candidate leads.

HTS laboratories continue to show year to year success at
producing new drug candidates. Fifty-five directors from HTS
laboratories participating in this recently published study, High
Throughput Screening 2007: New Strategies, Success Rates and Use of
Enabling Technologies, identified 163 drug candidates that originated
from their HTS laboratories, a significant increase from HighTech
Business Decisions' earlier study. With new HTS laboratories funded
through NIH or other private foundations beginning to ramp-up their
operations, this new report includes analysis and data from interviews
with HTS laboratory directors at these centers to better understand
their plans and their impact on drug discovery efforts.

William Downey, President of HighTech Business Decisions,
explains, "HTS laboratories are taking on new challenges as they
expand their role in drug discovery. In the past two years, the
industry has seen consolidation in HTS laboratories as many
pharmaceutical companies have either merged or acquired other
operations. This consolidation along with the challenges to improve
drug discovery efforts is leading to changes in the way particular HTS
laboratories operate. In addition to the changes in commercial HTS
laboratories, over the past two years publicly funded and
non-commercial HTS laboratories have been started, and in the next few
years these laboratories will ramp-up their operations." HighTech
Business Decisions extensively interviewed 55 Directors at HTS
laboratories in Asia, Europe and North America.

Sunnyvale, CA November 15, 2007 - Labcyte Inc. will supply Burnham Institute for Medical Research (Burnham) with more than $2.3 million worth of Echo® liquid handlers for use in screening large biological libraries. The systems will be installed at both the Institute’s LaJolla, (CA) and Lake Nona, Orlando (FL) campuses. These instruments will be part of the world’s largest screening system and will bolster Burnham’s research and drug discovery efforts, which include research on cancer, neurological diseases, aging, diabetes, and obesity.

Burnham is one of the nation’s 10 collaborating centers of excellence funded under a special initiative created by the National Institutes of Health, which together comprise the largest public-sector drug discovery effort in history. The state-of-the-art Labcyte technology will improve screening results while reducing operating costs for Burnham and the collaborating network advancing this historical effort. The systems will be delivered over the next six months.

“The Echo liquid handlers were selected because their unique acoustic technology will enhance our ability to miniaturize assays, reduce compound waste, and meet throughput requirements,” explained Dr. Stefan Vasile, Director of the Chemical Library Screening Facility for Burnham Institute. “The Echo systems will be used for compound plate-to-plate transfer, reformatting, dose-response experiments and hit picking.”

“Our patented acoustic droplet ejection technology dramatically reduces waste while cutting operating expenses,” said Dr. Elaine J. Heron, Labcyte CEO. “Traditional liquid handlers are prone to poor precision and accuracy as transfer volumes are decreased. Researchers who require flexibility in their processes and biology find that the Echo systems provide that for them easily, quickly, and cost-effectively.”

Labcyte Inc., headquartered in Sunnyvale, California, is the world leader in providing acoustic droplet ejection technology for pharmaceutical and life science applications. The award-winning Echo 500 series liquid handlers and Portrait 630 reagent multi-spotters are used in nine of the 10 largest pharmaceutical companies, as well as in leading academic and research institutions and contract research organizations worldwide. The Labcyte acoustic droplet ejection technology has broad applications including compound management, assays, arraying, particle manufacturing, imaging mass spectrometry, and live-cell transfer. Labcyte also provides a range of unique microplate consumables. Labcyte has 29 issued U.S. patents, 3 issued European patents and additional international filings. For more information, visit www.labcyte.com

HTS techniques have become an important part of the drug discovery process allowing researchers to sift through massive libraries of compounds to find ‘hits’ that are active against a therapeutic target of interest.

This latest research, published as an early view article in the journal Analytical Chemistry by researchers from the Discovery Technologies and Diabetes and Metabolism divisions of Novartis‘ Institute for Biomedical Research, has assessed the usage of MS-HTS for large compound library screening.

Most functional activity-based programmes discover hits by detecting a change in the activity of a target enzyme in the presence of potential inhibitors or activators.

These changes in activity are commonly detected by using substrates that have been labelled with either radioisotopes or fluorescent probes.

According to the authors, labelled substrates do not always function exactly the same as native substrates and the developing methods to incorporate these labels can add significantly to method-development times.

MS can detect the products of enzymatic reactions without the need to label the substrates and the authors believe that this could potentially improve data quality achieved using the screens.

However, according to the authors, until recently throughput has been the major limiting factor in using MS for HTS and while using multiple instruments could be used to solve the problem, this would prove expensive.

“One contributing factor to the lack of large-scale [MS-HTS] studies is that instrumentation allowing unattended, fully automated analysis of thousands of samples per day with automated data analysis is not readily available,” write the authors.

The researchers looked at three different MS-HTS techniques, four-way parallel multiplexed electrospray liquid chromatography (LC) tandem MS (MUX-LC/MS/MS), four-way parallel staggered gradient liquid chromatography tandem MS (LC/MS/MS) and eight-way staggered flow injection MS/MS following 384-well plate solid phase extraction (SPE).

Each of these methods makes use of parallel autosamplers to enable more efficient use of the Waters Quattro Micro triple quadrupole MS instruments.

The techniques described in the paper allowed unattended analyses of screens of over 175,000 compounds, with a 384-well plate taking around 2 hours to analyse.

The researchers conducted two inhibitor screening campaigns using the techniques to show that they could be used reliably to detect inhibition of an (unnamed) enzyme by compounds in a library.

“In comparison to ultra-HTS methods (>100,000 wells per day), these MS methods are relatively slow (<10,000 wells per day), making single compound screening of more than 1m compounds impractical at this time,” write the authors.

However, because the screens require no custom labelling of reagents or the development of assays to measure labelling success considerable time can be saved during the method development phase.

When combined with ‘multiple compound per well’ screens that can increase analysis times by a factor of five, the MS screens compare favourably to traditional HTS methods.

“Although the MS analysis is relatively slow, overall timelines of MS-based screens from concept to hit list are similar to those of traditional HTS and ultra-HTS-based screens,” conclude the authors.

Researchers from Novartis have published results using high-throughput screening (HTS) mass spectrometry (MS) techniques for the identification of enzyme inhibitors.

HTS techniques have become an important part of the drug discovery process allowing researchers to sift through massive libraries of compounds to find ‘hits’ that are active against a therapeutic target of interest.

This latest research, published as an early view article in the journal Analytical Chemistry by researchers from the Discovery Technologies and Diabetes and Metabolism divisions of Novartis‘ Institute for Biomedical Research, has assessed the usage of MS-HTS for large compound library screening.

Most functional activity-based programmes discover hits by detecting a change in the activity of a target enzyme in the presence of potential inhibitors or activators.

These changes in activity are commonly detected by using substrates that have been labelled with either radioisotopes or fluorescent probes.

According to the authors, labelled substrates do not always function exactly the same as native substrates and the developing methods to incorporate these labels can add significantly to method-development times.

MS can detect the products of enzymatic reactions without the need to label the substrates and the authors believe that this could potentially improve data quality achieved using the screens.

However, according to the authors, until recently throughput has been the major limiting factor in using MS for HTS and while using multiple instruments could be used to solve the problem, this would prove expensive.

“One contributing factor to the lack of large-scale [MS-HTS] studies is that instrumentation allowing unattended, fully automated analysis of thousands of samples per day with automated data analysis is not readily available,” write the authors.

The researchers looked at three different MS-HTS techniques, four-way parallel multiplexed electrospray liquid chromatography (LC) tandem MS (MUX-LC/MS/MS), four-way parallel staggered gradient liquid chromatography tandem MS (LC/MS/MS) and eight-way staggered flow injection MS/MS following 384-well plate solid phase extraction (SPE).

Each of these methods makes use of parallel autosamplers to enable more efficient use of the Waters Quattro Micro triple quadrupole MS instruments.

The techniques described in the paper allowed unattended analyses of screens of over 175,000 compounds, with a 384-well plate taking around 2 hours to analyse.

The researchers conducted two inhibitor screening campaigns using the techniques to show that they could be used reliably to detect inhibition of an (unnamed) enzyme by compounds in a library.

“In comparison to ultra-HTS methods (>100,000 wells per day), these MS methods are relatively slow (<10,000 wells per day), making single compound screening of more than 1m compounds impractical at this time,” write the authors.

However, because the screens require no custom labelling of reagents or the development of assays to measure labelling success considerable time can be saved during the method development phase.

When combined with ‘multiple compound per well’ screens that can increase analysis times by a factor of five, the MS screens compare favourably to traditional HTS methods.

“Although the MS analysis is relatively slow, overall timelines of MS-based screens from concept to hit list are similar to those of traditional HTS and ultra-HTS-based screens,” conclude the authors.