CRM1 inhibitor, orally bioavailable and selective
CAS：1393477-72-9
分子式：C17H11F6N7O
分子量：443.31
纯度：98%
存储：Store at -20°C

Background:

KPT-330, analog of KPT-185, is a selective inhibitor of CRM1 [1].

Chromosomemaintenance protein 1 (CRM1) is a nuclear export receptor involved in the active transport of transcription factors, cell-cycle regulators, tumor suppressors and RNA molecules. In cancer, CRM1 is overexpression and overactive transport [1].

KPT-330 is an orally bioavailable and selective CRM1 inhibitor. In kidney cancer (RCC) cells, KPT-330 inhibited CRM1 and increased nuclear localization of p21. Then, KPT-330 induced apoptosis and inhibited cells growth [2]. In human non-small cell lung cancer (NSCLC) cells, KPT-330 inhibited cell proliferation and induced the expression of apoptosis-related proteins and cell cycle arrest [3].

In mice bearing MiaPaCa-2 xenograft model, KPT-330 (20 mg/kg) significantly inhibited tumor growth without significant toxicity or body weight loss. Also, KPT-330 increased PAR-4, pro-apoptotic Bax, cleaved PARP and caspase-3. These results suggested that KPT-330 induced apoptosis by the activation of PAR-4 signaling [1]. In mice bearing human NSCLC xenografts, KPT-330 significantly inhibited tumor growth [3].

参考文献:
[1].? Azmi AS, 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.
[2].? Wettersten HI, Landesman Y, Friedlander S, et al. Specific inhibition of the nuclear exporter exportin-1 attenuates kidney cancer growth. PLoS One, 2014, 9(12): e113867.
[3].? Sun H, Hattori N, Chien W, et al. KPT-330 has antitumour activity against non-small cell lung cancer. Br J Cancer, 2014, 111(2): 281-291.