Biochem/physiol Actions

MS436 is a diazobenzene-based potent BRD4 inhibitor with selective affinity toward the first bromodomain (BrD) of BRD4 (BRD4 BrD1 Ki ﹤85 nM vs. BRD4 BrD2 Ki = 340 nM; IC50 = 460 nM/BRD4 BrD1 vs. 1.29 µM/BRD4 BrD2, 4.95 µM/CBP BrD, 20.29 µM/PCAF BrD). MS436 is a useful tool for probing BRD4-dependent cellular functions, including NF-κB-mediated proinflammatory response in RAW264.7 murine macrophages (IC50 in µM = 4.9/3.8 against LPS-induced IL-6/NO production), human and murine embryonic stem cell (ESC) pluripotency maintenance (10 µM), telomere elongation in mTERT/mTR-overexpressing murine fibroblasts (5 µM), and bioenergetic deficiency caused by mitochondrial complex I (CI)-mutation in human cybrid cells (0.9 µM).