AZD5991 is a macrocyclic MCL-1 inhibitor with sub-nanomolar affinity for MCL-1 (Ki = 0.13 nM). The binding affinity of AZD5991 is about 25-fold lower for mouse Mcl-1 vs. human Mcl-1 but only four-fold lower for rat Mcl-1.
Storage Temp
Store at -20°C
Shipped In
Ice chest + Ice pads
Grade
Moligand™
Action Type
INHIBITOR
Mechanism of action
Inhibitor of MCL1 apoptosis regulator; BCL2 family member
Product Description
Information
AZD5991 AZD5991 is a macrocyclic MCL-1 inhibitor with sub-nanomolar affinity for MCL-1 (Ki = 0.13 nM). The binding affinity of AZD5991 is about 25-fold lower for mouse Mcl-1 vs. human Mcl-1 but only four-fold lower for rat Mcl-1.
AZD5991 is a potent and direct inhibitor of Mcl-1 with high selectivity versus other Bcl-2 family proteins. AZD5991 binds directly to Mcl-1 and induces rapid apoptosis in cancer cells, most notably myeloma and acute myeloid leukemia (GI50 < 100nM), by activating the Bak-dependent mitochondrial apoptotic pathway. In a panel of cancer-derived cell lines of hematological or solid tumor origin, AZD5991 preferentially kills hematological cells.
In vivo
AZD5991 shows potent antitumor activity in vivo with complete tumor regression in several models of multiple myeloma and acute myeloid leukemia after a single tolerated dose as monotherapy or in combination with bortezomib or venetoclax. In these in vivo studies, the cytotoxic activity of AZD5991 tightly correlates with induction of the mitochondrial apoptotic pathway as evidenced by cleavage of caspase-3 and PARP.
Cell Research(from reference)
Cell lines：MOLP-8 cells
Concentrations：0-500 nM
Incubation Time：30 min
Associated Targets(Human)
MCL1TchemInduced myeloid leukemia cell differentiation protein Mcl-1 (2 Activities)
1.Tron AE, Belmonte MA, Adam A, Aquila BM, Boise LH, Chiarparin E, Cidado J, Embrey KJ, Gangl E, Gibbons FD et al.. (2018) Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia.. Nat Commun, 9 (1):(5341). [PMID:30559424][10.1021/op500134e]
2.Denis C, Sopková-de Oliveira Santos J, Bureau R, Voisin-Chiret AS. (2020) Hot-Spots of Mcl-1 Protein.. J Med Chem, 63 (3):(928-943). [PMID:31580668][10.1021/op500134e]
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