Birabresib (MK-8628) is a synthetic, small molecule inhibitor of the BET (Bromodomain and Extra-Terminal) family of bromodomain-containing proteins 2, 3 and 4 with potential antineoplastic activity.

BRDs:10-19 nM(EC50)

Birabresib抑制BRD2、BRD3和BRD4与AcH4的结合，IC50值在92至112 nM之间，且抑制多种人类癌细胞系的增长，GI50值在60至200 nM范围内。[1] Birabresib迅速下调c-MYC表达，并在与ALK抑制剂联合使用时，对ALKpos ALCL细胞系显示出协同的抗增殖效应。[2]

OTX015 (p.o.) 在裸鼠体内有效抑制Ty82 BRD-NUT中线癌肿瘤的生长，分别在每日一次100 mg/kg和每日两次10 mg/kg的剂量下，抑制率达到79%和61%。[1]

TR-FRET Assay [1]: To assess binding of OTX015 to BRD2, BRD3, and BRD4, BRD-expressing CHO cell lysate (from CHO cells transfected with expression plasmids for Flag-tagged BRD2, BRD3, or BRD4 or vector alone), europium-conjugated anti-Flag antibody, XL-665-conjugated streptavidin, and biotinylated OTX015 are incubated at room temperature for 0.2 to 2 h. Fluorescence is measured by TR-FRET using an EnVision 2103 Multilabel Reader and EC50 for binding is calculated by nonlinear regression using PRISM version 5.02.

Effects of OTX015 on cancer cell proliferation are evaluated by incubating human tumor cells for 72 h with increasing concentrations of OTX015 and assessing proliferation using a tetrazolium salt (WST-8)-based colorimetric assay.(Only for Reference)