AZD5153 6-Hydroxy-2-naphthoic acid

A potent, selective, bivalent and orally available BET/BRD4 bromodomain with IC50 of 5 nM; simultaneously binds to two bromodomains in BRD4; exhibits antitumor activity in multiple xenograft models of acute myeloid leukemia, multiple myeloma, and diffuse large B cell lymphoma. (In Vitro) :AZD5153 demonstrates a remarkable enhancement in potency for the displacement of full-length BRD4 relative to BD1, with IC50 values of 5.0 nM and 1.6 μM, respectively. AZD5153 potently disrupts BRD4 foci in U2OS cells with an IC50 value of 1.7 nM. AZD5153 efficiently down-regulates MYC protein levels across the cell line panel irrespective of their sensitivity to AZD5153. (In Vivo) :Administration of AZD5153 leads to tumor stasis or regression in multiple xenograft models of acute myeloid leukemia, multiple myeloma, and diffuse large B-cell lymphoma. AZD5153 treatment markedly impacts transcriptional programs of MYC, E2F, and mTOR.