DRB

A classic inhibitor of transcription by RNA polymerase II. A relatively selective inhibitor of Cdk9 (IC50=3 μM), the kinase of the positive transcription elongation factor b (P-TEF-b) required for processive transcription elongation by RNA polymerase II [1,2]. Also inhibits casein kinase II, IC50=4-10 μM [3]. Suppresses the SIRT1/CK2α pathway and enhances the radiosensitivity of human cancer cells [4]. Kinase-independent activities of Cdk9 such as glucocorticoid receptor modulation are not inhibited by DRB [5].

References:

1) Baumli et al. (2010), Halogen bonds form the basis for selective P-TEFb inhibition by DRB; Chem.Biol., 17 931

2) Yamaguchi et al. (1998), Interplay between positive and negative elongation factors: drawing a new view of DRB; Genes Cells, 3 9

3) Zandomeni  (1989), Kinetics of inhibition by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole; Biochem.J., 262 469

4) Wang et al. (2014), Inhibition of P-TEFb by DRB suppresses SIRT1/CK2α pathway and enhances radiosensitivity of human cancer cells; Anticancer Res., 34 6981

5) Zhu et al. (2014), A kinase-independent activity of Cdk9 modulates glucocorticoid receptor-mediated gene induction; Biochemistry, 53 1753