1402141-72-3

Upstream product

• 1402141-70-1 5-(4-chlorophenyl)-2-methyl-4-(3-(4-(4-nitrophenyl)piperazin-1-yl)phenyl)-1-propyl-1H-pyrrole-3-carboxylic acid 
• 1402141-68-7 ethyl 5-(4-chlorophenyl)-2-methyl-4-(3-(4-(4-nitrophenyl)piperazin-1-yl)phenyl)-1-propyl-1H-pyrrole-3-carboxylate 
• 1402141-66-5 ethyl 5-(4-chlorophenyl)-4-(3-iodophenyl)-2-methyl-1-propyl-1H-pyrrole-3-carboxylate 
• 1384513-05-6 ethyl 2-acetyl-4-(4-chlorophenyl)-3-(3-iodophenyl)-4-oxobutanoate 
• 1027345-07-8 4-fluoro-3-(trifluoromethylsulfonyl)benzene-1-sulfonyl chloride 

Downstream Products

• 1391106-71-0 (R)-5-(4-chlorophenyl)-4-(3-(4-(4-(4-(4-(4-hydroxypiperidin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonamido)phenyl)piperazin-1-yl)phenyl)-2-methyl-1-propyl-1H-pyrrole-3-carboxylic acid 

Relevant academic research and scientific papers

Structure-based discovery of BM-957 as a potent small-molecule inhibitor of Bcl-2 and Bcl-xL capable of achieving complete tumor regression

Bcl-2 and Bcl-xL antiapoptotic proteins are attractive cancer therapeutic targets. We have previously reported the design of 4,5-diphenyl-1H-pyrrole-3- carboxylic acids as a class of potent Bcl-2/Bcl-xL inhibitors. In the present study, we report our structure-based optimization for this class of compounds based upon the crystal structure of Bcl-xL complexed with a potent lead compound. Our efforts accumulated into the design of compound 30 (BM-957), which binds to Bcl-2 and Bcl-xL with Ki 50 values in cell growth inhibition in cancer cell lines. Significantly, compound 30 achieves rapid, complete, and durable tumor regression in the H146 small-cell lung cancer xenograft model at a well-tolerated dose schedule.