abt-737 and Carcinoma--Non-Small-Cell-Lung

abt-737 has been researched along with Carcinoma--Non-Small-Cell-Lung* in 1 studies

Other Studies

1 other study(ies) available for abt-737 and Carcinoma--Non-Small-Cell-Lung

Article	Year
Structure-based discovery of BM-957 as a potent small-molecule inhibitor of Bcl-2 and Bcl-xL capable of achieving complete tumor regression. Journal of medicinal chemistry, 2012, Oct-11, Volume: 55, Issue:19 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 K(i) < 1 nM and has low nanomolar IC(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. Topics: Animals; Antineoplastic Agents; bcl-X Protein; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Crystallography, X-Ray; Drug Screening Assays, Antitumor; Humans; Lung Neoplasms; Mice; Mice, SCID; Neoplasm Transplantation; Protein Conformation; Proto-Oncogene Proteins c-bcl-2; Pyrroles; Stereoisomerism; Structure-Activity Relationship; Sulfonamides; Tumor Burden	2012

Article

Year

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

Journal of medicinal chemistry, 2012, Oct-11, Volume: 55, Issue:19

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 K(i) < 1 nM and has low nanomolar IC(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.

Topics: Animals; Antineoplastic Agents; bcl-X Protein; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Crystallography, X-Ray; Drug Screening Assays, Antitumor; Humans; Lung Neoplasms; Mice; Mice, SCID; Neoplasm Transplantation; Protein Conformation; Proto-Oncogene Proteins c-bcl-2; Pyrroles; Stereoisomerism; Structure-Activity Relationship; Sulfonamides; Tumor Burden

2012