BM-1197

BM-1197 (UBX1967) is a potent and selective inhibitor of dual Bcl-2/Bcl-xL, with IC₅₀s of 3.5 nM and 5.2 nM for Bcl-2 and Bcl-xL, respectively. BM-1197 exhibits antitumor effects both in vitro and in vivo^[1][2]. In Vitro: BM-1197 (2-2000 nM; 3 d) has marginal cytotoxicity against wild-type mouse embryonic fibroblast (MEF) cells but exerts potent growth-inhibitory activity in the MCL1^?/? cells^[1].
BM-1197 shows potent growth-inhibitory activities in 7 small cell lung cancer (SCLC) cell lines with IC₅₀s <100 nM, moderate activity in 3 SCLC cell lines with IC₅₀s of ～600 nM and weak activity in 2 SCLC cell lines with IC₅₀s >2000 nM^[1].
BM-1197 (100 nM; 16 h) potently induces apoptosis in H146 cells^[1].
BM-1197 (100 nM; 2 h) disrupts the association between Bcl-xl and Puma or Bim in H146 cells^[1].
BM-1197 (100 nM; 0.5-2 h) induces Bax translocation, and it (3-30 nM; 2 h) induces cytochrome c release in H146 cells^[1]. In Vivo: BM-1197 (10 mg/kg; i.v. daily 5 days per week for 2 weeks) results in rapid and complete tumor regression in all 8 mice in H146 and H1963 tumor model^[1].
BM-1197 (15 mg/kg; i.v.) causes thrombocytopenia in mice but the effect is reversible even at highly efficacious doses^[1].
BM-1197 (10 mg/kg; i.v. qd) exerts a strong anti-tumor effect and is well tolerated in OCI-Ly8 xenograft models^[2].