1H-Pyrrole-3-carboxamide, 5-[5-chloro-2-[[(3S)-3,4-dihydro-3-(4-morpholinylmethyl)-2(1H)-isoquinolinyl]carbonyl]phenyl]-N-(5-cyano-1,2-dimethyl-1H-pyrrol-3-yl)-N-(4-hydroxyphenyl)-1,2-dimethyl-

Biological Activity

S65487 (VOB560) is a potent and selective Bcl-2 inhibitor. S65487 is also active on BCL-2 mutations, such as G101V and D103Y. S65487 has poor affinity with MCL-1, BFL-1 and BCL-XL. S65487 induces apoptosis and has anticaner activities[1][2]. S65487 binds to the BH3 hydrophobic groove of BCL-2. S65487 induces apoptosis in a panel of hematological cancer cell lines and inhibits cell proliferation with IC50s in the low nM range[1]. S65487 induces complete regression in BCL-2-dependent RS4;11 tumors in vivo after a single IV (intravenous) administration. Strong and persistent tumor regression in xenograft models of lymphoid malignancies in mouse and rat are observed at well tolerated doses following weekly IV administration of S65487 in combination with the MCL-1-specific inhibitor, S64315/MIK665[1].

References

[1]. Arnaud Le Tiran, et al. Abstract 1276: Identification of S65487/VOB560 as a potent and selective intravenous 2nd-generation BCL-2 inhibitor active in wild-type and clinical mutants resistant to Venetoclax. Cancer Research. July 2021. [2]. American Association for Cancer Research, AACR. 2021.4.10-15.