Scientists discover class of potent anti-cancer compounds

Working as part of a public program to screen compounds to find potential medicines and other biologically useful molecules, scientists from The Scripps Research Institute and Massachusetts Institute of Technology (MIT) have discovered an extremely potent class of potential anti-cancer and anti-neurodegenerative disorder compounds. The scientists hope their findings will one day lead to new therapies for cancer and Alzheimer's disease patients.

The research-published in the journal Proceedings of the National Academies of Sciences (PNAS) the week of March 7, 2011-was led by Benjamin F. Cravatt III, professor and chair of the Department of Chemical Physiology at Scripps Research and a member of its Skaggs Institute for Chemical Biology, and MIT chemistry professor Gregory Fu.

''It was immediately clear that a single class of compounds stood out,'' said Daniel Bachovchin, a graduate student in the Cravatt lab and the study's first author. ''The fact that these compounds work so potently and selectively in cancer cells and mice, right off the screening deck and before we'd done any medicinal chemistry, is very encouraging and also very unusual.''

Browsing in the Public Library
The National Institutes of Health (NIH) Common Fund Molecular Libraries Program currently funds nine screening and medicinal chemistry-related centers at academic institutions around the United States to enable scientists to find biologically interesting molecules, independently of commercial labs (http://mli.nih.gov/mli/mlpcn/mlpcn-probe-production-centers/). In these centers, academic scientists can test thousands of compounds at once through high-throughput screens against various biological targets to uncover "proof-of-concept" molecules useful in studying human health and in developing new treatments for human diseases.

''Initially the compounds in the NIH Molecular Libraries repository were purchased from commercial sources and augmented through chemical diversity initiatives,'' explained Ingrid Y. Li, director of the Molecular Libraries Program at the NIH National Institute of Mental Health (NIMH). ''In recent years we've also encouraged academics to donate structurally unusual compounds, to add novelty to the library.'' (See http://mli.nih.gov/mli/compound-repository/.)

In 2008, Fu's lab donated a set of molecules known as aza-beta-lactams (ABLs)- molecular cousins of penicillin and other beta-lactam antibiotics. ''These were molecules that probably didn't exist in commercial compound libraries, and their bioactivity had been virtually unexplored,'' said Fu.