BM-1074

BM-1074 is a potent and specific Bcl-2/Bcl-xL inhibitor with Ki values of < 1 nM and IC50 values of 1.8 nM and 6.9 nM for Bcl-2 and Bcl-xL, respectively. BM-1074 induces apoptosis, and exhibits antiproliferative activity against four small-cell lung cancer cell lines (H146, H1963, H187 and H1417) with IC50 values of 1-2 nM[1].

Signaling Pathways >> Apoptosis >> Bcl-2 Family

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Bcl-2:1.8 nM (IC50)

Bcl-xL:6.9 nM (IC50)

BM-1074 (Compound 32) shows high binding affinity to both Bcl-2 and Bcl-xL proteins and exhibits inhibitory activity against H146, H1963, H187, and H1417 cell lines[1]. Cell Proliferation Assay[1] Cell Line: H146, H1963, H187, and H1417 Concentration: 0-200 nM Incubation Time: 4 days Result: Inhibited the cell growth of H146, H1963, H187 and H1417 cell lines with IC50 values of 1.3 nM, 1.0 nM, 1.4 nM and 2.3 nM, respectively.

BM-1074 (i.v., 15 mg/kg, daily, 5 days a week for 2 weeks) exhibits the maximum tolerated dose (MTD) (15 mg/kg) and strong antitumor activity in H146 tumor xenograft mice, as well as shows no significant weight loss (<5%) or other signs of toxicity[1]. BM-1074 (i.v., 15 mg/kg, single dosage) induces strong apoptosis in H146 tumor tissues[1]. Animal Model: SCID mice (injected with 5 x 106 H146 cancer cells with Matrigel, subcutaneously)[1] Dosage: 15 mg/kg Administration: i.v., 15 mg/kg, daily, 5 days a week for 2 weeks Result: Showed good toleration and did not cause significant weight loss or other signs of toxicity, also induced completely and persistent tumor regression in the H146 xenograft model. Animal Model: SCID mice (injected with 5 x 106 H146 cancer cells with Matrigel, subcutaneously)[1] Dosage: 15 mg/kg Administration: i.v., 15 mg/kg, single dosage Result: Induced robust cleavage of PARP and caspase-3 at both 3 and 6-hr time-points in H146 tumor tissues.

[1]. Angelo Aguilar, et al. A potent and highly efficacious Bcl-2/Bcl-xL inhibitor. J Med Chem. 2013 Apr 11;56(7):3048-3067.