Bromodomain and Extra-Terminal Inhibitors Pipeline Analysis, 2017

The study analyzed that the BET inhibitors pipeline comprised 38 drug candidates, of which 19 were in Pre-Clinical stage of development. The high prevalence of cancer across the globe fuels the extensive research and development for BET inhibitors. BET inhibitor constitutes that class of drugs, which prevents interactions between BET proteins, and transcription factors and acetylated histone. This results in immunosuppressive and anti-cancer properties of BET inhibitor. Inhibition of BET proteins offered a new therapeutic approach for the treatment of cancer, cardiovascular diseases and other diseases.

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Insights on pipeline segments

As per the findings of the research, around 16% of BET inhibitor drug candidates target BRD4 and 63% of the product candidates target BET. Other targets constituting 21% of candidates of the BET inhibitors pipeline include, but are not limited to, BRD2, BRD3, BRDT, Dual BET/DRD2, PI3K, super enhancer complex (SEC) and JAK2. Around 44% BET inhibitor pipeline drug candidates are being developed to be administered by oral route, and 3% by subcutaneous route.

IC50 value and Kd of different types of BET inhibitors

In BET inhibitors, IC50 value is measured as the concentration of drug at which 50% of the target is inhibited. IC50 is a pharmacokinetic measure; the lower the IC50 of drug candidate, the lesser the desired effect, and the less likelihood of the drug to have some off-target effect. Kd is known as dissociation constant of drug. It measures the rate of dissociation of the drug and its binding affinity. Birabresib (MK8628), a BET inhibitor by Merck & Co., has IC50 value of 100nM.

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Strategic collaborations for the development of BET inhibitors

The research finds that different companies are collaborating for the development of BET inhibitors. In January 2017, ConverGene entered into a sponsored research agreement with the University of Maryland, Baltimore. Under this agreement, University of Maryland School of Medicine Professor Curt I. Civin, M.D., who is associate dean for research and director of the Center for Stem Cell Biology & Regenerative Medicine, will investigate the in vivo anti-leukemic effects of ConverGene’s lead BET inhibitor drug candidates, CG223 and CG250. Some of the key players developing BET inhibitors are Resverlogix Corp., GlaxoSmithKline plc, Bristol-Myers Squibb Company, F. Hoffmann-La Roche Ltd., Merck & Co., Inc., AstraZeneca plc, Gilead Sciences, Inc., Zenith Epigenetics Ltd., and Incyte Corporation.

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