The Center focuses on “bench to bedside” collaborations and supports biomedical research by providing small molecules (probes) to elucidate physiology and pathophysiology, and to validate targets for drug discovery. The Center is well-equipped with its own major instruments (e.g., NMR, LC/MS, HPLCs, SPR) and it has current staff of 8 Ph.D. organic chemists. Since October 2006, the OCCC has contributed chemists and chemistry leadership to the NIH-funded comprehensive Molecular Libraries Screening Center at Columbia University (CU-MLSC), functioning as its Chemistry Core.  Over the past 4 years the OCCC has collaborated with over 20 biomedical research groups and synthesized an extensive array of compounds in support of over 25 projects.  These projects cover a wide range of biological research areas and disease states, with the major effort in each project focused on “hit-to-lead” optimization for drug or probe development.  Some efforts, excluding MLSC projects, include:

• Compounds that stabilize the calcium release channel and thereby prevent heart failure;
• BBB-penetrable PDE-5 inhibitors for Alzheimer’s disease;
• Isoform-selective PK inhibitors for treatment of chronic pain;
• Inhibitors of the ABAD-A-beta interaction of Alzheimer’s disease ;
• Steroid-sugar analogs that are inhibitors of A-beta peptide production to treat Alzheimer’s disease ;
• Inhibitors of the renal sodium-glucose co-transporter to treat diabetes and obesity; and
• An agent with a capacity for cytoprotection for myocardial ischemia and reperfusion injury.

In addition to drug discovery, the OCCC has synthesized small molecules as probes for other medicinal chemistry studies, for example: agents for labeling ion channels; agents for photoaffinity; labeling agents for the identification of a novel cholesterol transport protein, a novel target for anti-cholesterol drug development ; agents eliciting protection from nerve agents ; cocaine antibodies to cure overdose and addiction ; and the isolation and structure determination of mammalian siderophores from human tissue.
These collaborations have resulted in publications in top tier journals including Science , Circulation , PNAS , and JBC with manuscripts pending in Cell and Nature Medicine.  In addition, 12 patents were filed and the Center has been a pivotal resource for a number of successful NIH grants, including P01, R01, and R21 awards, and Columbia University’s Roadmap Clinical and Translational Science Award (1 of the first 12 awarded) as well as for the CU Molecular Libraries Screening Center itself.  Additionally, three startup companies have been formed based on “leads” initially discovered at the OCCC: 1) ARMGO Pharmaceuticals (May 2006) to commercialize compounds stabilizing the calcium release channel for the treatment of heart failure; 2) Nociceptive Pharmaceuticals (2006) to commercialize PKG inhibitors as a novel treatment for chronic pain; and 3) Smart Biosciences (2005) to commercialize a novel small-molecule approach to Alzheimer’s Disease.  At ARMGO, the lead compounds synthesized at the OCCC demonstrated both high potency and off-target selectivity as well as high efficacy in rodent models.  The lead compound will enter clinical trials both in the E.U. and in the U.S. in early 2008 as a joint effort with the large French pharmaceutical concern Servier.  At Nociceptive Pharmaceuticals, the lead compound synthesized at the OCCC showed low nanomolar inhibitory activity for PKG with a >200-fold selectivity over PKA, a structurally very similar kinase.  The lead compound also showed efficacy in animal models for pain relief (see the Preliminary Studies section below).

The compounds designed and synthesized in this center was covered twice by Chemical & Engineering News:

April 12 issue of 2004 and

Feb 18 issue of 2008