Mechanism of action: BRD4/BET bromodomain antagonist

Preclinical pharmacology

AZD5153 is a bivalent BRD4/BET bromodomain inhibitor with a cellular target engagement IC50 of 1.7nM monitoring BRD4 displacement from super-enhancers and IC50~ 5nM in modulating BRD4 target genes such as MYC and CCR2.

AZD5153 exhibits potent growth inhibition activity (< 100 nM) in majority of hematologic tumor cell lines and ~50% of solid tumor cell lines with diverse tumors’ tissue of origin.

AZD5153 monotherapy shows significant anti-cancer activity in hematologic and solid tumor xenograft models in vivo.

AZD5153 combination therapies demonstrated synergistic anti-cancer activity with select SOCs and targeted agents in vitro and in vivo

Suitable for and exclusions

Restricted to preclinical oncology studies (proposals) only

Additional Information

Molecular Cancer Therapuetics

Journal of Medicinal Chemistry

Clinical Cancer Research

Nature Chemical Biology

Gene information from the NCBi

This compound works on the following genes: