HO-3867是一种新的姜黄素类似物,是STAT3的选择性抑制剂.[1]

STAT3(信号转导和转录激活子3)属于STAT蛋白家族.STAT3介导用于多种细胞功能的各种基因的表达,包括细胞生长\分裂和凋亡.

HO-3867可选择性阻断STAT3磷酸化\转录和DNA结合,而不抑制其他STAT蛋白.该物质可在卵巢癌细胞中激活细胞凋亡,对健康细胞有最低毒性.[2]HO-3867也可显著抑制血清刺激的SMC增殖,并可提高SMC中磷酸化的和总的PTEN水平.[3]HO-3867可通过诱导细胞周期停滞和细胞凋亡,降低子宫内膜癌细胞中高水平的pSTAT3 Ser727.[4]

在小鼠肿瘤异种移植物中,HO-3867可抑制肿瘤生长而不引起毒性副作用,该物质也可阻断PSTAT3/JAK1,并可提高凋亡标志物剪切的Caspase 3/PARP.[2][5]在大鼠颈动脉受伤后,HO-3867可抑制内膜增生,并能上调PTEN表达.[3]

参考文献：
[1] Tierney BJ, McCann GA, Cohn DE, Eisenhauer E, Sudhakar M, Kuppusamy P, Hideg K, Selvendiran K.  HO-3867, a STAT3 inhibitor induces apoptosis by inactivation of STAT3 activity in BRCA1-mutated ovarian cancer cells. Cancer Biol Ther. 2012 Jul;13(9):766-75.
[2] Rath KS, Naidu SK, Lata P, Bid HK, Rivera BK, McCann GA, Tierney BJ, Elnaggar AC, Bravo V, Leone G, Houghton P, Hideg K, Kuppusamy P, Cohn DE, Selvendiran K. 
HO-3867, a safe STAT3 inhibitor, is selectively cytotoxic to ovarian cancer.  Cancer Res. 2014 Apr 15;74(8):2316-27.
[3] Selvendiran K, Kuppusamy ML, Bratasz A, Tong L, Rivera BK, Rink C, Sen CK, Kálai T, Hideg K, Kuppusamy P.  Inhibition of vascular smooth-muscle cell proliferation and arterial restenosis by HO-3867, a novel synthetic curcuminoid, through up-regulation of PTEN expression. J Pharmacol Exp Ther. 2009 Jun;329(3):959-66.
[4] Tierney BJ, McCann GA, Naidu S, Rath KS, Saini U, Wanner R, Kuppusamy P,Suarez A, Goodfellow PJ, Cohn DE, Selvendiran K.  Aberrantly activated pSTAT3-Ser727 in human endometrial cancer is suppressed by HO-3867, a novel STAT3 inhibitor. Gynecol Oncol. 2014 Oct;135(1):133-41.
[5] Selvendiran K, Tong L, Bratasz A, Kuppusamy ML, Ahmed S, Ravi Y, Trigg NJ, Rivera BK, Kálai T, Hideg K, Kuppusamy P.  Anticancer efficacy of a difluorodiarylidenyl piperidone (HO-3867) in human ovarian cancer cells and tumor xenografts. Mol Cancer Ther. 2010 May;9(5):1169-79.