Peng X, Xie G, Wang Z, Lin H, Zhou T, Xiang P, Jiang Y, Yang S, Wei Y, Yu L, Zhao Y
1] State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China [2] Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China.
Cell Death Dis. 2014 Mar 27;5(3):e1143. doi: 10.1038/cddis.2014.107.
Small-molecule inhibitors are an attractive therapeutic approach for most types of human cancers. SKLB-163, a novel benzothiazole-2-thiol derivative, was developed via computer-aided drug design and de novo synthesis. MTT assay showed it had potent anti-proliferative activity on various human cancer cells. Treatment of cancer cells with SKLB-163 induced obvious apoptosis and inhibited proliferation in vitro. SKLB-163 administered p.o. showed a marked antitumor activity in vivo. Proteomic techniques were employed to identify possible drug target proteins. The data showed molecular mechanism of action might be involved in downregulation of RhoGDI, which finally contributed to increased apoptosis and inhibited proliferation. These findings provided the potential value of SKLB-163 as a novel candidate antitumor drug.
小分子抑制剂对大多数类型的人类癌症来说是一种有吸引力的治疗方法。SKLB-163是一种新型苯并噻唑-2-硫醇衍生物，通过计算机辅助药物设计和从头合成而开发。MTT试验表明它对各种人类癌细胞具有强大的抗增殖活性。用SKLB-163处理癌细胞可诱导明显的凋亡并在体外抑制增殖。口服给予SKLB-163在体内显示出显著的抗肿瘤活性。采用蛋白质组学技术来鉴定可能的药物靶蛋白。数据表明其作用分子机制可能涉及RhoGDI的下调，这最终导致凋亡增加和增殖受到抑制。这些发现提供了SKLB-163作为一种新型候选抗肿瘤药物的潜在价值。
