AZD-5991, an antitumor compound, is a highly selective, potent and direct MCL-1 inhibitor that induces rapid apoptosis in cancer cells by activating the Bak-dependent mitochondrial apoptotic pathway, used for multiple myeloma, acute myeloid leukemia, and triple-negative inflammatory breast cancer.

McL1:0.7 nM, McL1:0.17 nM (Kd)

Methods: A panel of MCL cell lines were treated with AZD-5991 (10-1000 nM, 24 hours) and cell viability was measured using the CellTiter-Glo cell viability assay (Promega).
Results: MCL cell lines that were sensitive or resistant to ibrutinib or venetoclax were sensitive to AZD-5991 (IC50 values ​​ranged from 69.3 to 523.5 nM), with Mino showing particularly high sensitivity to AZD-5991. [2]

Methods: MOLP-8 tumor model mice were treated with AZD-5991 (10-100 mg/kg, intravenous injection) and the efficacy of AZD-5991 on MOLP-8 tumor growth in vivo was evaluated.
Results: AZD-5991 produced dose-dependent antitumor effects ranging from tumor growth inhibition (TGI) to tumor regression (TR). After ten days of treatment, AZD-5991 showed a TGI of 52% and 93% at 10 and 30 mg/kg, respectively (p < 0.0001). [1]