Rigosertib

Rigosertib是磷酸肌醇3-激酶(PI3K)和polo样激酶1(PLK1)的双重抑制剂[1].

体外研究表明,在人白血病细胞中,Rigosertib抑制PI3K/AKT途径\下调cyclin D1\诱导NOXA和BIM,并激活JNK途径.Rigosertib诱导多种人类肿瘤细胞系的凋亡,包括乳腺癌\前列腺癌\卵巢癌\胰腺癌\小细胞肺癌\结直肠癌和黑色素瘤等.例如,Rigosertib对BT20\MCF-7\BT474\OV-CAR-3\A549和HCT-116均具有抗肿瘤作用,相应IC50值为80 nM\75 nM\50 nM\75 nM\90 nM和75 nM.此外,Rigosertib对耐药肿瘤细胞系也显效.在MES-SA/DX5和CEM/C2中,Rigosertib有效抑制肿瘤生长,其IC50值分别为100 nM和50 nM.据报道,Rigosertib可以影响正常细胞以及肿瘤细胞的细胞周期.在正常二倍体人胚肺细胞中,Rigosertib使细胞周期进展阻滞于G1和G2/M期.在DU145细胞中,Rigosertib诱导细胞周期停滞于G2/M期[2].

参考文献：
[1] Anderson R T, Keysar S B, Bowles D W, et al.  The Dual Pathway Inhibitor Rigosertib Is Effective in Direct Patient Tumor Xenografts of Head and Neck Squamous Cell Carcinomas. Molecular cancer therapeutics, 2013, 12(10): 1994-2005.
[2] Reddy M V R, Venkatapuram P, Mallireddigari M R, et al.  Discovery of a clinical stage multi-kinase inhibitor sodium (E)-2-{2-Methoxy-5-[(2′, 4′, 6′-trimethoxystyrylsulfonyl) methyl] phenylamino} acetate (ON 01910. Na): synthesis, structure–activity relationship, and biological activity. Journal of medicinal chemistry, 2011, 54(18): 6254-6276.