AZD 5153 an orally available, bivalent inhibitor of the bromodomain and extraterminal (BET) protein BRD4 (IC50 = 5 nM). It can simultaneously bind two bromodomains in BRD4, which has been shown to increase antitumor activity in multiple xenograft models of acute myeloid leukemia, multiple myeloma, and diffuse large B cell lymphoma.
a quantitative immuno-fluorescent assay in u2os cells revealed that azd5153 could significantly disrupt brd4 foci, with the ic50 value of 1.7 nm. besides, azd5153 could inhibit the proliferation of aml, mm, and dlbcl cell lines, with the majority of cell lines having a gi50 value < 25 nm. furthermore, 200 nm azd5153 could significantly decrease the level of mtor pathway associated proteins in sensitive hematologic cancer cell lines (molp8, mv-4-11, ocily19) [1].
in aml, mm, and dlbcl xenografted tumor mouse models, oral administration of azd5153 at the dose of 1, 2.5, and 5mg/kg could inhibit tumor growth in a dose dependent manner [1].
[1] rhyasen g w, hattersley m m, yao y, et al. azd5153: a novel bivalent bet bromodomain inhibitor highly active against hematologic malignancies[j]. molecular cancer therapeutics, 2016, 15(11): 2563-2574.
