Bio Screening Industry News

Sirona Biochem Corp. (TSX-V: SBM), an emerging biotech company focused on diabetes and obesity, says results of testing its unique SGLT inhibitor molecules demonstrate a key breakthrough milestone for Sirona Biochem.

Sirona Biochem CEO, Dr. Howard Verrico, said, “There are two vital steps in the early stage of drug testing: validation of concept i.e. a molecule is able to hit the desired target and secondly its in vivo effectiveness. This first round of testing has shown a key breakthrough milestone in the process of validating this concept.”

“The test results now mean we can proceed to find out whether the molecules are selective, safe and robust enough to have potential to be effective when they reach the parts of the body where the re-uptake of glucose needs to be limited.”

Dr. Bertrand Plouvier, Chief Scientist, said, “The results from the first round of screening are indeed very encouraging and Sirona Biochem will use the next following months to further study the molecules through specific assays to demonstrate their effectiveness and drug likeness.”

Dr. Verrico said management of sugar metabolism is a primary medical challenge associated with treating diabetes and obesity and that is why SGLT inhibitors show such promise in this regard. “At present SGLT2 inhibitors have demonstrated their ability to limit the re-uptake of glucose back into the blood stream from urine. However, they have been notoriously lacking in ability to resist being rapidly metabolized by the body, thus rendering them largely ineffective.

“What we have now done is show that our molecules, with their unique GlycoMim® technology, can inhibit the glucose transporter SGLT2. The next challenge, and an exciting one, is to show that our molecules are selective, safe and have the potential to have an increased efficacy compared to the current molecules undergoing clinical development.”

Sirona Biochem owns the worldwide product rights to a library of unique sodium glucose transporter (SGLT) inhibitors to treat diabetes and obesity. SGLT inhibitors, as previously stated, block the re-uptake of excess sugars from urine, which can then reduce high blood sugar towards normal levels.

Sirona Biochem has entered into a strategic partnership with TFChem, a drug discovery company based in Rouen, France. TFChem licenses its technology of fluorinated carbohydrate mimics: GlycoMim®, and products in development to biotech companies. This strategic partnership was completed by a detailed research and licence agreement signed on September 29, 2008.

23.6 million people, or 7.8% of the population of the United States, have diabetes. (February 2009 DACG.ORG)

Market Trends

In 2007, the prevention and treatment of diabetes and its complications was estimated to cost US$ 232 billion according to the International Diabetes Federation. By 2025, this is likely to increase to more than US$ 302.5 billion.

The diabetes drug market reached US$18 billion in 2005, and is expected to increase to $21-25 billion in 2011. With many new products yet to realise their full potential and the high incidence of T2DM expected in emerging markets, prospects for the sector look strong. Some of the fastest growing markets for diabetes are in emerging economies. India, China and Indonesia are in the top 5 for disease prevalence. The impact for both branded and generic drugs is considerable.

Furthermore, in recent years, obesity has become a major health problem for many post-industrial societies, so much so that in 2004, the United States Health and Human Services declared obesity to be a disease. The World Health Organization (WHO) projects that globally in 2005, 1.6 billion adults were overweight with at least 400 million adults obese. By 2015, approximately 2.3 billion adults will be overweight and 700 million will be obese. Obesity poses a major health risk because it greatly increases the risk of co-morbidities such as diabetes, cardiovascular diseases, arthritis, and cancer. Recognizing the potential for a new blockbuster market, major pharmaceutical companies have increasingly focused on obesity and its causes and, in the process, seeking to identify many potential targets and pathways that could be exploited to create novel therapies.

Sirona Biochem’s website is at: www.sironabiochem.com where we feature the most recent information about the company and its activities. Alternatively, investors are able to e-mail all questions and correspondence to info@sironabiochem.com where they can also request to be added to the investor e-mail list to receive all future press releases and updates or call John Dougherty, Corporate Development at 604-641-4466.

About Sirona Biochem

Sirona Biochem Corp. (TSX-V: SBM) is an emerging biotech company dedicated to the discovery and development of novel drug compounds. The current focus is on treatments for Type II diabetes and obesity. Sirona has entered into a license agreement with TFChem S.A.R.L., a drug discovery company based in Rouen, France. TFChem licenses its technology of fluorinated carbohydrate mimics: GlycoMim®, and products in development to biotech companies. The license agreement with TFChem provides for research and development of new compounds known as SGLT Inhibitors. SGLT inhibitors are a new and exciting class of compounds that have great promise and potential to treat both diabetes and obesity.

Mark Senner
President and Director

Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.

BioLeap and GSK have entered into an agreement whereby BioLeap will design novel
lead compounds for "difficult" drug targets. The targets (not disclosed) are
ones for which conventional approaches, like high throughput screening, have
failed to yield a viable chemical starting point. Typically these are in areas
of high unmet medical need.

BioLeap will use its computational fragment-based drug design platform to
conceive compounds de novo that are molecularly tailored to bind to the target.
GSK will synthesize and test the compounds in biochemical and cellular assays.
The process will iterate until GSK selects a Lead Candidate. The terms of the
agreement for services were not disclosed.

David Pompliano, PhD, CEO of BioLeap said, "We are very pleased to be working
with GSK to accelerate the discovery of truly novel medicines. BioLeap`s
platform reliably predicts the effect of compound modifications on target
affinity, thus minimizing unproductive guesswork during drug discovery, and
producing a better drug candidate more quickly."

About BioLeap

BioLeap is a leader in computational fragment-based drug design. The company`s
proprietary design technology and process successfully addresses one of the
biggest problems in pre-clinical drug discovery: the limitation of drug like and
patentable leads for important biological targets. BioLeap is using its
completely "in-silico" platform to quickly and accurately predict
fragment-protein binding information that provides drug designers new insights
that enable them to efficiently create new and improved drug molecule
candidates. The BioLeap computational approach addresses the time, cost, and low
probability of success limitations imposed by traditional library screening and
lead optimization methods. BioLeap is utilizing its capabilities to advance its
own internal preclinical stage programs while collaboratively enabling
non-competing programs with numerous pharmaceutical partners.

Source: reuters.com

Last October, TimTec and Collaborative Drug Discovery (CDD) established a collaboration in which CDD’s web-based data management system would host two TimTec Natural Products libraries on their free community Public Access site.  Through this partnership, researchers would be able to register for a free account with CDD allowing them to chemically mine the contents of these TimTec compound libraries using CDD’s powerful, intuitive web-based database software.

TimTec is now offering three more libraries on the CDD Public Access database:

The TimTec ActiTarg-K Kinase Modulators library contains over 6,000 compounds known to inhibit protein kinase activity:

http://www.timtec.net/actitarg-k-kinase-modulators.html

The TimTec OGT Inhibitors Analogs library contains more than 300 compounds analogous to three known O-GlcNAc Transferase inhibiting molecules:

http://www.timtec.net/o-glcnac-transferase-inhibitors.html

Finally, the TimTec resourceful Diversity Set is a general screening collection of drug-like compounds that present most diversified selection from TimTec stock. This screening library contains 10,000 of the most diverse compounds, all complying with the Lipinski Rule of Five:

http://www.timtec.net/diversity-set-10k.html

TimTec’s five databases join more than 25 other databases containing chemical and biological data hosted on CDD Public Access, including:

• 47,000 Ki values for 20,000 compounds against 699 GPCR targets from the NIMH Psychoactive Drug Screening Program at the University of North Carolina
• Over 15,000 compounds with Malaria assay data from 5 public data sources
• 48,818 compounds from the Distributed Drug Discovery (D3) at Indiana University – Purdue University Indianapolis (IUPUI)
• Almost 7,500 compounds with Tuberculosis antibacterial and cell viability information from 4 public data sets and growing thanks to their collaboration with the Bill & Melinda Gates Foundation

About TimTec, LLC.

TimTec LLC. - http://www.timtec.net - is a privately held company located in NewarkDelaware, USA. It was founded in 1995 and began its work in the areas of acquisition and distribution of synthetic organic and natural compounds, custom synthesis, and laboratory equipment to become a full service partner for drug discovery. TimTec has established a global network of thousands of scientists from research centers around the world. The company has developed strong in-house expertise assembling general and targeted library collections for variety of research purposes. International customers include major pharmaceutical, biotech, agricultural, and educational companies and institutions, which use TimTec products for research and development programs.

For more information on TimTec library collections, please contact:

Kay Denisova
Business Development
TimTec LLC
Harmony Business Park Building 301-A
Newark, DE 19711
Tel 302 292 8500
Fax 302 292 8520
info(at)timtec.net
http://www.timtec.net

About Collaborative Drug Discovery, Inc.

Collaborative Drug Discovery, Inc. (CDD) - http://www.collaborativedrug.com - provides web-based software that organizes preclinical research data to help scientists advance new drug candidates more effectively. The CDD database enables scientists to “archive, mine, and collaborate”® around preclinical chemical and biological drug discovery data through a web-based interface. The software helps distributed research groups to safely store and intelligently analyze small molecule, enzyme, cell and animal bioactivity data accumulated from both low-throughput and high-throughput screens. Unique collaboration features and CDD’s community-oriented approach help unite globally dispersed humanitarian efforts against neglected infectious diseases. Similar collaborative strategies are also rapidly gaining prominence in the commercial arena. CDD offers its industrial-strength database software at a price affordable to academic laboratories, research foundations, and small companies.

For further information please contact:

Barry Bunin, PhD
President & CEO
Collaborative Drug Discovery (CDD)
1633 Bayshore Hwy, Suite 342
Burlingame, CA 94010
info(at)collaborativedrug.com

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 “Small Molecule Screening Libraries in Drug Discovery: Experience and Trends”.

The official language of the symposium is English.

http://www.ldorganisation.com

Thermo Fisher Scientific, the world leader in serving science, announced recently that it has introduced a novel tool to accelerate hit-to-lead programmes in the drug discovery process. Its Maybridge Quick2Lead™ Compound Kits are designed to save time and money by enabling rapid compound library synthesis around bioactive “hits” emerging from screening assays. The kits are made up of pre-weighed, diverse building block selections, facilitating rapid capture of structure-activity (SAR) data from the closely related structural analogues within the library.

Quick2Lead Compound Kits are available as five functionality-based kits, with each one containing 48 carefully selected compounds. This enables the exploration of a wide area of chemical space to maximise credible SAR data acquisition for the successful conversion of an initial hit into a genuine, optimisable lead. Since these compounds are all pre-weighed, the kits are ready to use by simply adding solvent and transferring straight to a synthesiser.

The five functional groups available include: carboxylic acids, sulfonyl chlorides, amines, anilines and boronic acids. Each of these different functional groups is applicable to a wide range of tried and trusted parallel synthesis methodologies. Furthermore, although each kit taps into the hugely diverse Maybridge collection, they all include compounds from the top levels of the relevant Topliss Tree, thereby ensuring quality and rigour in interaction testing.

Each of the pre-selected compounds is supplied as 0.1mMol in a 5mL vial. This saves time and money at several levels — minimising stock, avoiding disposal and reducing storage footprint. The pre-selection process also avoids the “dead time” that can be experienced whilst waiting for multiple building blocks from internal and external sources. Maybridge Quick2Lead Kits arrive as a complete library, delivered rapidly ex-stock.

“Our aim with the Maybridge product range is to help shorten the discovery process, from screening to scale-up, and the introduction of our Quick2Lead Compound Kits is the latest addition to our broad product portfolio of pharmacophorically relevant compounds and services,” said Dr. Mick Durrant, Director of Business Development for Maybridge products at Thermo Fisher Scientific. “We recognise that identifying, sourcing and weighing building blocks to feed the library production process around an initial hit can be time consuming and expensive. Our new Quick2Lead Kits offer a novel approach to drive these costs down by providing pre-weighed, diverse building block selections which are simply ready-to-go.”

About Maybridge
Maybridge, part of Thermo Fisher Scientific, is well known for providing highly innovative drug-like molecules and screening compounds for drug discovery and development. With products available for both lab and development scale, they specialise in producing new heterocyclic and phenyl ring-based chemical building blocks, including a unique and expanding range of reactive intermediates.

About Thermo Fisher Scientific
Thermo Fisher Scientific Inc. is the world leader in serving science, enabling our customers to make the world healthier, cleaner and safer. With annual revenues of $10.5B, we have more than 34,000 employees and serve over 350,000 customers within pharmaceutical and biotech companies, hospitals and clinical diagnostic labs, universities, research institutions and government agencies, as well as environmental and industrial process control settings. Serving customers through two premier brands, Thermo Scientific and Fisher Scientific, we help solve analytical challenges from routine testing to complex research and discovery. Thermo Scientific offers customers a complete range of high-end analytical instruments as well as laboratory equipment, software, services, consumables and reagents to enable integrated laboratory workflow solutions. Fisher Scientific provides a complete portfolio of laboratory equipment, chemicals, supplies and services used in healthcare, scientific research, safety and education. Together, we offer the most convenient purchasing options to customers and continuously advance our technologies to accelerate the pace of scientific discovery, enhance value for customers and fuel growth for shareholders and employees alike.

SOURCE: Thermo Scientific Brand Products, Part of Thermo Fisher

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.

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

Hamburg, Germany | Oxford, UK | Oslo, Norway - Evotec AG (Frankfurt Stock Exchange: EVT) 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 bio-logical 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 com-bined 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 investi-gations 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 capabili-ties. 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 Næss-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.

New Hope, PA — (SBWIRE) — 10/10/2007 — Bucks County’s Institute for Hepatitis and Virus Research (IHVR) and BioLeap have entered into a collaboration to develop new therapeutic compounds for the treatment of Hepatitis C. Up to 50% of patients treated with current standard therapies do not respond adequately and often suffer serious side effects from the drugs. Thus there is a critical need for new tools to treat this disease. By combining BioLeap’s leading edge computational fragment-based design capabilities with the IHVR’s extensive experience and in-depth knowledge of viral diseases, the collaboration will result in new classes of lead drug molecules with novel modes-of-action.

Of particular interest to the IHVR is BioLeap’s proprietary technology that rapidly calculates the free energies, or affinities of interactions between small molecular fragments of potential drugs and biomolecular structures of the proteins they will target, displaying the distribution and orientation of these fragments. This information provides a unique insight into how small molecules bind into key protein binding sites that cannot be achieved from the static crystal structure alone, or from methods that can only measure the enthalpic properties of binding. In addition to lead discovery, the quantitative free-energy based analysis of protein-drug-fragment interactions adds significant value to the lead optimization process. In combination, this proprietary approach provides chemists and biologists the information they need to assemble, fragment by fragment, a completely new molecule that not only optimally binds to the targeted protein site but also has properties desirable in a drug, including solubility and bioavailability.

Commenting on the collaboration, BioLeap’s Gerry Evans, Executive Vice President of BioLeap, noted: “Dr. Tim Block and his team at the IHVR are renowned for their work in this field. We are very excited by the opportunity to focus our combined expertise on this important target.”

Dr. Tim Block, president of the IHVR, is enthusiastic about the prospects for this collaboration. “One approach in discovering new treatments is the time and labor intensive process of screening tens or hundreds of thousands of molecules from compound libraries. BioLeap’s technology provides a potential shortcut by eliminating the need to screen compound libraries, while significantly broadening the field of chemical diversity. The molecules designed by BioLeap are not limited by what is present in any compound library. This greatly increases our odds of finding a potential drug that precisely targets the hepatitis C virus and that will not easily succumb to viral resistance. Once BioLeap has identified several candidate molecules, our scientists will test their effectiveness on the hepatitis C virus. Based on these results, we will repeat this iterative process until we have found the ideal drug.”

About the Institute for Hepatitis and Virus Research:
Established as the research arm of the Hepatitis B Foundation, the mission of the Institute for Hepatitis and Virus Research is to use discovery science to find new therapies for viral hepatitis and liver cancer; to advance its research discoveries through traditional scholarship and educational opportunities; to nurture biotechnology through technology transfer and new company formation; and to promote public health outreach programs to improve the quality of life for those with viral hepatitis.

About BioLeap:
Bioleap is a leader in computational fragment-based drug design. The company’s proprietary design technology and process successfully addresses one of the biggest problems in preclinical drug discovery: limited chemical diversity of compound libraries. Development collaborations span a broad spectrum of target proteins including: kinases, nuclear hormone receptors, metalloenzymes, and metalloproteases.