A dual inhibitor of IGF-1R and IR
BMS-536924 is a novel inhibitor of IGF-1R with IC50 value of 100nM [1].
It has been found that BMS-536924 has cell toxicity in OVCAR-3 and OVCAR-4 cell lines. BMS-536924 inhibits cell proliferation partly via reducing phosphorylations of AKT and ribosomal protein S6, one of AKT’s downstream targets. [2].
BMS-536924 also induces apoptosis in vitro as indicated by the elevation of PARP-1 cleavage. It can induce DNA damage by the manner of increasing the phosphorylated histone H2AX as well as increasing the tail moment observed in the comet assay. It thus sensitizing cells to PARP inhibition [2].
参考文献:
[1] Mark G. Saulnier, David B. Frennesson, Mark D. Wittman, Kurt Zimmermann, Upender Velaparthi, David R. Langley, Charles Struzynski, Xiaopeng Sang, Joan Carboni, Aixin Li, Ann Greer, Zheng Yang, Praveen Balimane, Marco Gottardis, Ricardo Attar and Dolatrai Vyas. 2-(1H-Imidazol-4-yl)ethanamine and 2-(1H-pyrazol-1-yl)ethanamine side chain variants of the IGF-1R inhibitor BMS-536924. Bioorganic & Medicinal Chemistry Letters. 2008 (18):1702-1707.
[2] Marie-Claude Beauchamp, Ariane Knafo, Amber Yasmeen, Joan M. Carboni, Marco M. Gottardis, Michael N. Pollak, Walter H. Gotlieb. BMS-536924 sensitizes human epithelial ovarian cancer cells to the PARP inhibitor, 3-aminobenzamide. Gynecologic Oncology. 2009 Aug (115):193-198.
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