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

S65487 hydrochloride engages with the BH3 hydrophobic groove of BCL-2, effectively inducing apoptosis in various hematological cancer cell lines while concurrently inhibiting cell proliferation. Its inhibitory concentration 50 (IC50s) values are in the low nanomolar (nM) range[1].

S65487 hydrochloride effectively induces complete regression of BCL-2-dependent RS4;11 tumors in vivo with just one intravenous (IV) administration. When administered weekly via IV at doses well tolerated by the organism, a combination of S65487 hydrochloride and the MCL-1-specific inhibitor, S64315/MIK665, results in strong and persistent regression of lymphoid malignancy xenograft models in both mice and rats[1].