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- W4361959211 abstract "<div>Abstract<p>BMS-754807 is a potent and reversible inhibitor of the insulin-like growth factor 1 receptor/insulin receptor family kinases (Ki, <2 nmol/L). It is currently in phase I development for the treatment of a variety of human cancers. BMS-754807 effectively inhibits the growth of a broad range of human tumor types <i>in vitro</i>, including mesenchymal (Ewing's, rhabdomyosarcoma, neuroblastoma, and liposarcoma), epithelial (breast, lung, pancreatic, colon, gastric), and hematopoietic (multiple myeloma and leukemia) tumor cell lines (IC<sub>50</sub>, 5–365 nmol/L); the compound caused apoptosis in a human rhabdomyosarcoma cell line, Rh41, as shown by an accumulation of the sub-G<sub>1</sub> fraction, as well as by an increase in poly ADP ribose polymerase and Caspase 3 cleavage. BMS-754807 is active <i>in vivo</i> in multiple (epithelial, mesenchymal, and hematopoietic) xenograft tumor models with tumor growth inhibition ranging from 53% to 115% and at a minimum effective dose of as low as 6.25 mg/kg dosed orally daily. Combination studies with BMS-754807 have been done on multiple human tumor cell types and showed <i>in vitro</i> synergies (combination index, <1.0) when combined with cytotoxic, hormonal, and targeted agents. The combination of cetuximab and BMS-754807 <i>in vivo</i>, at multiple dose levels, resulted in improved clinical outcome over single agent treatment. These data show that BMS-754807 is an efficacious, orally active growth factor 1 receptor/insulin receptor family–targeted kinase inhibitor that may act in combination with a wide array of established anticancer agents. [Mol Cancer Ther 2009;8(12):3341–9]</p></div>" @default.
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- W4361959211 date "2023-03-31" @default.
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- W4361959211 title "Data from BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R/IR" @default.
- W4361959211 doi "https://doi.org/10.1158/1535-7163.c.6531836" @default.
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