BM-1197

Research use only, not for human use.

BM-1197 is a potent, specific dual inhibitor of Bcl-2 and Bcl-xL with Ki of <1 nM.

BM-1197 is a potent, specific dual inhibitor of Bcl-2 and Bcl-xL with Ki of <1 nM, shows >1,000-fold selectivity over Mcl-1; exerts potent growth-inhibitory activity in 7 of 12 small cell lung cancer cell lines tested and induces mechanism-based apoptotic cell death, induces complete and long-lasting tumor regression in vivo.

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.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.BM-1197 (100 nM; 16 h) potently induces apoptosis in H146 cells.BM-1197 (100 nM; 2 h) disrupts the association between Bcl-xl and Puma or Bim in H146 cells.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.Cell Proliferation Assay Cell Line:MEF/MCL1?/? cells Concentration:2, 20, 200, 2000 nM Incubation Time:3 days Result:Inhibited MCL1?/? cells proliferation.Apoptosis Analysis Cell Line:H146 cells Concentration:100 nM Incubation Time:16 hours Result:Induced apoptosis in a strictly Bax/Bak-dependent manner.Western Blot Analysis Cell Line:H146 cells Concentration:100 nM Incubation Time:2 hours Result:Attenuated the associations between Bcl-xL and BimEL or Puma.

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.BM-1197 (15 mg/kg; i.v.) causes thrombocytopenia in mice but the effect is reversible even at highly efficacious doses.BM-1197 (10 mg/kg; i.v. qd) exerts a strong anti-tumor effect and is well tolerated in OCI-Ly8 xenograft models. Animal Model:SCID mice bearing H146 cells Dosage:10 mg/kg Administration: I.v. daily 5 days per week for 2 weeks Result:Remained tumor free for at least 32 days after the end of the treatment.

BM1197

Angiogenesis

Bcl-2

Bcl-2

——

——

1391107-89-3

1131.774

C53H59ClF4N6O7S4

>98% (HPLC)

In Vitro:?DMSO : 250 mg/mL (220.89 mM)

——

N-[4-[4-[3-[2-(4-Chlorophenyl)-5-methyl-1-(1-methylethyl)-4-(methylsulfonyl)-1H-pyrrol-3-yl]-5-fluorophenyl]-1-piperazinyl]phenyl]-4-[[(1R)-3-(4-hydroxy-1-piperidinyl)-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoromethyl)sulfonyl]benzenesulfonamide

(-20℃)

With Ice Pack

≥ 2 years