Validation of Targets
To understand how NCATS will help further catalyze drug development, consider just one of the ongoing NIH programs slated to move into this new center: the Molecular Libraries Probe Production Centers Network (MLPCN). Created as part of the 2004 NIH Roadmap for Medical Research,8 MLPCN established the first federally funded network to facilitate drug discovery by producing early-stage small molecule leads.9
These centers, most of which reside in universities and nonprofit research institutes across the U.S., provide federally funded researchers and even small biotechnology companies with access to drug discovery capabilities previously found only within large pharmaceutical companies. Those capabilities include large chemical libraries, assay development, ultra high-throughput robotic screening, cheminformatics, medicinal chemistry, project management, and several other drug discovery-related services that typically don’t exist in academic labs and departments.
The MLPCN initiative is probably too young for us to critically evaluate its impact on human health, but several unique opportunities are emanating from this federally funded enterprise. In MLPCN, academic researchers use chemical probes to explore a wide range of targets10 that are not yet validated to the satisfaction of the pharmaceutical industry.
As recently as 2006, the entire repertoire of approved drugs was determined to address only 324 targets, clearly indicating that further efforts are needed to generate chemical modulators of more targets. And there’s probably no better and more clinically relevant way to validate a target than with a chemical probe that modulates the activity of a disease-relevant protein.
Moreover, researchers interfacing with MLPCN are tackling many classes of targets largely ignored by pharmaceutical companies because they are considered technically challenging, and thus too risky for organizations that must worry about generating a return on R&D investments. The nonprofit, public-benefit research community has the flexibility to follow up on any interesting lead, no matter what the target or disease.
Not uncommonly, a MLCPN screening campaign with the objective of identifying antagonists of a particular target leads instead to the discovery of agonists—interesting compounds that can be pursued for different indications than originally envisioned. In contrast, a for-profit company screening for new drugs for a particular therapeutic area might be forced to leave findings that could cure another disease languishing on the shelf. Unfortunately, worries about the bottom line and demands from powerful marketing groups don’t always leave room for scientific curiosity.
Dr. Miller is right on one point—at the other end of the drug pipeline, the FDA approval process creates another bottleneck that keeps new medicines from reaching the market as quickly as we’d like. Here too, through NCATS, the NIH’s leadership is proposing a more robust partnership with the FDA to advance regulatory science.11 This way, FDA regulations can keep pace with the scientific innovations that are creating promising new opportunities to improve human health.
As it becomes increasingly difficult to obtain funding from any source, the infrastructure that allows nonprofit researchers to advance the next generations of innovative therapeutics and diagnostics is at risk of being lost. Without NCATS, many potential therapies will never reach the FDA in the first place, let alone the patients who need them. For this reason, I enthusiastically support the NIH’s newly proposed—and much-needed—National Center for Advancing Translational Sciences.