Results with thalidomide analogs published in the Proceedings of the National Academy of Science
DeuteRx, LLC, is a research and development-focused biotechnology company dedicated to improving racemic small molecule marketed drugs and drug candidates intended for patients across multiple therapeutic indications. DeuteRx hasannounced the discovery of a method for the in vivo stabilization and differentiation of the individual enantiomers of selected thalidomide analogs. The method is described in The Proceedings of the National Academy of Science (PNAS), entitled: "Differentiation of antiinflammatory and antitumorigenic properties of stabilized enantiomers of thalidomide analogs."
"Using our 'deuterium-enabled chiral switching' (DECS) platform, we enable the testing and development of the single, preferred enantiomer of certain drugs and drug-candidates that are currently developed or marketed as racemic mixtures (two mirror-image compounds or enantiomers). Historically, many stable, single enantiomer drugs have demonstrated improved therapeutic properties such as improved efficacy or reduced side effects over the parent racemic mixture. However, numerous drugs are still developed and marketed with racemic active ingredients because the enantiomers are chemically unstable and rapidly interconvert in vivo," said Sheila DeWitt, Ph.D., President & Chief Executive Officer of DeuteRx. "We have discovered and are developing stabilized enantiomers for several classes of compounds by replacing the exchangeable hydrogen at the chiral center with deuterium."
"Dr. DeWitt and her team have pioneered a novel approach to 'chiral switching', a successful and profitable strategy that initially emerged in the 1990s to develop the preferred, single, but stable enantiomer from a mixture of two stable enantiomers, resulting in many blockbuster drugs including Lexapro®, Lunesta®, Levaquin®, and Nexium®" said Timothy Barberich, Founder, Former Chairman, President & CEO to Sepracor (currently Sunovion Pharmaceuticals, Inc.) and advisor to DeuteRx.
In the publication, DeuteRx describes application of DECS to two thalidomide analogs, including CC-122, a compound currently in human clinical trials for hematological cancers and solid tumors. DeuteRx further shows that the in vitro antiinflammatory and in vivo antitumorigenic activity, in a mouse xenograft model of multiple myeloma, is due almost exclusively to the stabilized (-)-enantiomer of CC-122.
DeuteRx has eight issued U.S. patents with composition of matter claims encompassing deuterium-enriched enantiomers based on known racemic active ingredients. Additional pending patent applications by DeuteRx include claims to deuterium-enriched enantiomers for at least eleven families of thalidomide analogs, including CC-122.