Friday, February 26, 2010
Featured Article
Check out our Medicinal Chemistry Services section for more information or to find companies that provide these services.
It’s no secret that the pharmaceutical industry—like other industries—is farming out many of its essential drug discovery processes… and medicinal chemistry (medchem) is just one of them. Crucial to the success of a compound, medchem’s raison d’être is to optimize a compound’s performance so that it can reach the level of drug candidate. A medchem service provider, then, becomes the selection process by which compounds make the grade—or not. And such companies perform this duty in a variety of ways, many of which are described in this article.
The BioFocus Approach: Contracting to optimize compounds and access technologies absent in-house
As a company, BioFocus provides comprehensive drug discovery services, from discovering novel targets, to identifying the first compounds active against these targets, to performing medicinal chemistry optimization to clinical candidate drugs. With more than 80 chemists of its own working in a UK Research Park—and adding as many chemists through its acquisition of UK rival Argenta on February 2, 2010—the group is a powerful medicinal chemistry service provider. As such, Argenta and BioFocus essentially start their contracted drug discovery services with hit compounds that have come out of screening (within the group or from a client).
Optimization of a hit compound’s pharmacological properties to fit a candidate profile is performed by synthesizing chemical analogs of the parent molecule. Characteristics of the optimized compound include increased pharmacological potency on the biological target, pharmacokinetics (e.g. increased oral bioavailability), better toxicological properties, and intellectual property protection. “This process normally takes two to three years and several hundreds, if not thousands, of molecules are made along the way,” says Christopher G Newton, MA, MSc, PhD, CChem, FRSC, senior vice president of Galapagos Services and managing director of BioFocus, based at Chesterford Research Park, United Kingdom. BioFocus and Argenta have invested in technologies such as protein structure crystallography and polymorphism screening, that are available to clients as part of the optimization process. “We provide access to technologies for clients who may only need to use them from time to time—it's not cost-effective for them to build the technology in-house. Instead, they come to us to outsource the services,” says Newton.
Xceleron’s Approach: Optimizing Client Assets
Xceleron (Germantown, Md.) is not a pure medicinal chemistry service company. Instead, they “provide support to client assets coming out of medicinal chemistry, helping to optimize these assets and choosing those compounds that should be moved forward as a lead,” says Michael Butler, PhD, chief executive officer at Xceleron. Owner and supplier of a highly sensitive and highly specific analytical service for optimization or fine-tuning of client assets, Xceleron focuses much of its attention on testing all of its clients’ assets in humans. The reason for this human-only testing approach is that “current in vitro and in vivo systems employed by medicinal chemistry groups to screen hit compounds are not always sufficiently predictive,” says Butler. “The assets associated with contemporary drug targets require more screening directly in humans and that requires very low, safe doses that in turn require our ultra-sensitive analytical approach.”
“The biggest issue that our large pharma clients face is that there are too many compounds coming out of medicinal chemistry and making their way all the way to Phase 1 and Phase 2 and just not getting any further,” says Butler. “The problem is that the approaches that have been used in the past are not picking up on the fact that a compound is too insoluble and has poor bioavailability, for example.” Xceleron’s approach allows their clients to fail those compounds faster, and to more quickly move forward compounds that are successful. A rough estimate is that their approach is saving companies 7.5 to 10 million dollars and one to two years in time.
Aptuit’s Services; Forward-looking statements
Aptuit, Inc.’s services fall into two general categories: problem-solving and non-problem-solving. An example of a non-problem-solving service would be to just look at the properties of a given compound and give recommendations as to its future as a drug candidate. In a problem-solving scenario, there is a drug molecule that shows some potential, but has an issue with regard to solubility (e.g. a compound does not form a crystal) or bioavailability, which need to be improved by Aptuit. “Usually what our client wants us to do is to give recommendations as to what crystal form to put forward into drug development,” says Jan-Olav Henck, PhD, senior director, Aptuit, Inc., West Lafayette, Ind. To meet such client requests, Aptuit has developed a high-throughput screening tool that allows for powder x-ray diffractometry to be performed in 96-well plates in order to identify crystalline or amorphous material.
Henck also made a few statements regarding current and future trends in the medicinal chemistry services industry. Says Henck: “[Previously], generating high-quality data and then drawing conclusions and making recommendations based on these data were enough to sort of survive in this environment. In the future, however, it will be important to use computational methods that utilize the high-quality data to calculate or to estimate solid-state properties of a given compound in order to reduce the development timeline in the pharmaceutical development process. And this will be a very important distinguisher in the future for the kind of services that we offer.”
Check out our Medicinal Chemistry Services section for more information or to find companies that provide these services.