Research

From the Genome to Drugs

Medicinal Chemistry

Generating Diverse Drug-Like Compound Libraries
We use solution-phase chemistry to generate diverse libraries of optically pure compounds that are targeted against the same pharmaceutically relevant gene families that we addressed in our Genome5000™ program.  These libraries are built using highly robust and scalable organic reactions that allow us to generate compound collections of great diversity and to specially tailor the compound collections to address various therapeutic target families.  We design these libraries by analyzing the chemical structures of drugs that have been proven safe and effective against human disease and using that knowledge in the design of scaffolds and chemical building blocks for the generation of large numbers of new drug-like compounds. We have augmented our internally generated libraries with selected compounds from qualified vendors from around the world.  When we identify a hit against one of our in vivo-validated targets, we can rapidly reassemble these building blocks to create hundreds or thousands of variations around the structure of the initial compounds, enabling us to accelerate our medicinal chemistry efforts.

Selecting the Best Clinical Candidates
Our medicinal chemists optimize lead compounds in order to select clinical candidates that are potent and selective for the target of interest with the desired absorption, distribution, metabolism, excretion (ADME) and physicochemical characteristics of a drug.  We have the capability to pharmacologically profile our compounds using the same battery of in vivo assays that we use to characterize our drug discovery targets.  Throughout this process, the knockout mouse serves as an important guide in determining the on-target activity of our lead molecules.  This provides us with valuable, detailed information relevant to the selection of the highest quality compounds for preclinical and clinical development.

State-of-the-art Facilities
Our medicinal chemistry operations are located in Princeton, New Jersey.  Our lead optimization chemistry groups are organized around specific discovery targets and work closely with their pharmaceutical biology counterparts in our facilities in The Woodlands, Texas.