BM 957

It is found that 28 at 50 mg/kg, BM 957 at 25 mg/kg and 31 at 10 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 these compounds (75 mg/kg for 28, 50 mg/kg for 30 and 25 mg/kg for 31) cause more than 10% of weight loss. Mice bearing H146 tumors are given a single i.v. dose of 28 at 50 mg/kg or BM 957 at 25 mg/kg. It showed that although compound 28 at 50 mg/kg effectively inhibits tumor growth, it fails to induce tumor regression. In contrast, 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, both compounds 28 and BM 957 are 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 and is more efficacious than 28^[1].