BIO-0919278 RACEMATE

Biochem/physiol Actions

BIO-0919278 is a highly selective cyclin-dependent kinase CDK12 inhibitor (K_d = 5.6 µM) with little or no potency against CDK1-7, CDK9, CDK14, CDK16-18 or 344 other kinases (﹤35% inhibition at 1 µM). BIO-0919278 reduces CDK12-mediated Pol II CTD Ser2 phosphorylation (by 57% at 1 µM; U-2 OS cells) without affecting CDK12-independent Pol II CTD Ser5 phosphorylation, and selectively targets noncanonical NF-κB activation (4-hr 20 ng/mLTWEAK-induced p52 nuclear translocation/NIK mRNA production IC50 = 167/320 nM; U-2 OS cells) without affecting canonical NF-κB activation (TNF-α-stimulated p65 (RelA) nuclear translocation IC50 >30 µM).