Developing Small Molecules and Other Therapies for Drug Development

Center for Drug Discovery (320x240)
Center for Drug Discovery faculty include, from left to right, Drs. Martin Matzuk, Gwenn Hansen, Damien Young, Barry Morgan and Conrad Santini

Created in 2012, the Center for Drug Discovery is committed to helping investigators identify and develop compounds that will further their research pursuits and lead to new therapeutics. Dr. Martin M. Matzuk, the Stuart A. Wallace chair and professor of Pathology and Immunology at Baylor College of Medicine and a member of the National Academy of Sciences, is the director of the center.

The mission of the Center for Drug Discovery is to promote lead compound discovery and the creation of novel drugs for a wide range of illnesses, ranging from neurodegenerative diseases to infectious diseases to cancer. To reach these goals, the Center for Drug Discovery is recruiting outstanding investigators with diverse experiences in academia and industry to develop several seamless yet independent platforms. Currently, there are four state-of-the-art platforms that are being created within the center, and platforms 1 and 2 are unique in the State of Texas.

• Platform 1 is utilizing DNA-encoded, small-molecule library technology to create nearly 1 billion novel chemical compounds that are each uniquely linked to a DNA “tag.” Clinically important proteins are used to screen this chemical collection, and the DNA linked to these chemicals will identify the specific lead chemical compounds bound to each disease-related protein. Drs. Barry Morgan and Gwenn Hansen, experts in this technology, were recruited from the pharmaceutical industry to co-direct this platform.

Platform 2 uses fragment-based, diversity-oriented synthesis (DOS) technology to create a small, highly sophisticated library whose chemical compounds fill a larger three-dimensional space than do compounds in other libraries, thus making the fragments a better fit for their intended targets. Dr. Damian Young, a CPRIT scholar and world-class expert in this technology, leads this platform. The center recently has received funding support from a prestigious foundation to purchase a state-of-the-art, 800 MHz nuclear magnetic resonance (NMR) instrument to screen the Platform 2 fragment collections.

• Platform 3, led by Dr. Matzuk, involves assay development and high-throughput primary screening, including biophysical, biochemical, and cell-based screens of lead compounds. This platform also will undertake follow-up screens of optimized chemical compounds. 

Platform 4, whose group co-leaders are Dr. Young and Dr. Conrad Santini, who has decades of medicinal chemistry experience in the pharmaceutical industry, will use their skills in medicinal chemistry to make more potent analogs of the promising lead compounds.

At the present, the center is actively working with additional partnering investigators to integrate additional resources at Baylor, including X-ray crystallography, mass spectrometry, high-throughput microscopy of live cells, and kinetic screening that speeds the analysis of compounds against GPCRs and ion channels, and other technologies to augment the drug discovery process. With the platforms and existing technologies possessed by the Center for Drug Discovery, the team led by Dr. Matzuk is well poised to discover lead and optimized compounds that will be turned into drugs to combat previously inscrutable diseases and cancer targets.

BLG Project Manager

Brian Phillips, Ph.D. (bphillip@bcm.edu)