BM 957 is an effective Bcl-2 and Bcl-xL inhibitor (Kis: 1.2 and <1 nM; IC50s: 5.4 and 6.0 nM).

BCL-XL:1 nM (ki), BCL-XL:6.0 nM, BCL2:1.2 nM (ki), BCL2:5.4 nM

In these two cancer cell lines (H1417 and H146 cell lines), BM 957 has IC50 values of 21 nM and 22 nM, respectively. All these compounds induce cell death in a dose-dependent manner but have different potencies. While BM 957 and 31 are several times more potent than 1 and 2. BM 957 at 10 nM, 28 at 100 nM and 2 at 30 nM all induce clear cleavage of PARP and activation of caspase-3 and have similar effects.

It is found that BM 957 (Compound 30) at 25 mg/kg daily, intravenous dosing, 5 days a week for 2 weeks are well tolerated in SCID mice and the animals have less than 10% of weight loss. Higher doses of 50 mg/kg for BM 957 cause more than 10% of weight loss. Mice bearing H146 tumors are given a single i.v. the dose of BM 957 at 25 mg/kg. BM 957 at 25 mg/kg is capable of achieving complete tumor regression. Of 7 mice treated with BM 957, all mice are tumor-free at day 47 and five (71%) remained tumor-free on day 58. Similar to the data obtained from our MTD experiment, BM 957 is well-tolerated in tumor-bearing animals. All treated animals experienced less than 10% weight loss compared to the vehicle control and all regained their weight quickly after the treatments are finished. This in vivo experiment thus establish that BM 957 achieves complete and durable tumor regression in the H146 xenograft tumor model.