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Overview
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Please contact us at for specific academic pricing.
Background
KPT-185 is a selective and irreversible inhibitor of chromosome maintenance protein 1 (CRM1) with IC50 values of 100-500nM [1].CRM1 is an important nuclear protein export receptor. Blocking CRM1-mediated nuclear export can result in the suppression of tumors. As an inhibitor of CRM1, KPT-185 binds CRM1within the Cys528 site and prevents CRM1from interacting with tumor-suppressor proteins. In the in vitro studies on AML cell lines, KPT-185 inhibits proliferation of a variety of leukemia cells with IC50 values ranging from 100nM to 500nM. It induces cell-cycle arrest at G1 and induces apoptosis. KPT-185 also strongly affects cell colony formation. In addition, the inhibition of CRM1 caused by KPT-185 induces differentiation of AML blast. Besides that, KPT-185 is also found to inhibit proliferation and induce apoptosis of pancreatic cancer cells including Colo-357, HPAC and BxPC-3 [1, 2].
[1] Ranganathan P, Yu X, Na C, et al. Preclinical activity of a novel CRM1 inhibitor in acute myeloid leukemia. Blood, 2012, 120(9): 1765-1773.
[2] Azmi A S, Aboukameel A, Bao B, et al. Selective inhibitors of nuclear export block pancreatic cancer cell proliferation and reduce tumor growth in mice. Gastroenterology, 2013, 144(2): 447-456.
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