BET inhibitor

[1][2] Thienodiazepine BET inhibitors were discovered in a phenotypic drug screen by scientists at Yoshitomi Pharmaceuticals (now Mitsubishi Tanabe Pharma) in the early 1990s, and their potential both as anti-inflammatories and anti-cancer agents noted.

[3][4] OncoEthix (acquired by Merck in 2014) in-licensed OTX-015 from Mitsubishi and in 2012 initiated the first BET inhibitor clinical trial for oncology (ClinicalTrials.gov Identifier: NCT01713582).

BET inhibitors were also independently discovered in phenotypic screens for small molecule inducers of Apolipoprotein A-I by both GSK and Resverlogix.

[9] Only in the research context has targeting individual BET proteins been achieved by mutating them to be more sensitive to a derivative of JQ1 / I-BET 762.

[14][15][16] BRD2 and BRD3 are functionally redundant and may be more important as therapeutic targets than is appreciated in studies depleting each BET protein individually.