S65487 (VOB560) hydrochloride, a potent and selective Bcl-2 inhibitor, is effective against BCL-2 mutations, including G101V and D103Y. It exhibits poor affinity for MCL-1, BFL-1, and BCL-XL. This compound induces apoptosis and possesses anticancer activities.

S65487 hydrochloride binds to the BH3 hydrophobic groove of BCL-2. S65487 hydrochloride induces apoptosis in a panel of hematological cancer cell lines and inhibits cell proliferation with IC 50 s in the low nM range[1].

S65487 hydrochloride 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 hydrochloride in combination with the MCL-1-specific inhibitor, S64315/MIK665[1].