Mivebresib (ABBV-075) is a novel BET family bromodomain inhibitor. Binds to the bromodomain of BRD2/4/T with similar affinity (Ki values between 1-2.2 nM) with high selectivity. Low potency against BRD3 (Ki=12.2 nM) and moderate activity against CREBBP (Ki=87 μM). It can effectively trigger apoptosis in a variety of tumor cells.
ABBV-075 has potent and potent single-agent activity in a variety of cancer cell lines (from solid tumors, leukemias and lymphomas) in cell viability assays. It is capable of disrupting cell cycle control, leading to G1 arrest, further senescence, inhibition of tumor formation, induction of apoptosis, and possibly targeting the tumor microenvironment to further provide better efficacy.
In mouse models laterally xenografted with non-small cell and small cell lung cancer, pancreatic cancer, breast cancer, prostate cancer, head and neck cancer, multiple lymphomas, diffuse giant B-cell lymphoma, and leukemia, ABBV -075 has equal or better efficacy than other standard care agents.