A highly potent and selective farnesyltransferase inhibitor ABT-100 in preclinical studies

被引：8

作者：

Gu, WZ ^{[1
]}

Joseph, I ^{[1
]}

Wang, YC ^{[1
]}

Frost, D ^{[1
]}

Sullivan, GM ^{[1
]}

Wang, L ^{[1
]}

Lin, NH ^{[1
]}

Cohen, J ^{[1
]}

Stoll, VS ^{[1
]}

Jakob, CG ^{[1
]}

Muchmore, SW ^{[1
]}

Harlan, JE ^{[1
]}

Holzman, T ^{[1
]}

Walten, KA ^{[1
]}

Ladror, US ^{[1
]}

Anderson, MG ^{[1
]}

Kroeger, P ^{[1
]}

Rodriguez, LE ^{[1
]}

Jarvis, KP ^{[1
]}

Ferguson, D ^{[1
]}

Marsh, K ^{[1
]}

Ng, SC ^{[1
]}

Rosenberg, SH ^{[1
]}

Sham, HL ^{[1
]}

Zhang, HY ^{[1
]}

机构：

[1] Abbott Labs, Global Pharmaceut Res & Dev, Canc Res, Abbott Pk, IL 60064 USA

来源：

ANTI-CANCER DRUGS | 2005年 / 16卷 / 10期

关键词：

angiogenesis; animal model; crystal structure; farnesyltransferase inhibitor; Ras;

D O I：

10.1097/00001813-200511000-00004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Ras mutation has been detected in approximately 20-30% of all human carcinomas, primarily in pancreatic, colorectal, lung and bladder carcinomas. The indirect inhibition of Ras activity by inhibiting farnesyltransferase (FTase) function is one therapeutic intervention to control tumor growth. Here we report the preclinical anti-tumor activity of our most advanced FTase inhibitor (FTI), ABT-100, and a direct comparison with the current clinical candidates. ABT-100 is a highly selective, potent and orally bioavailable FTI. It broadly inhibits the growth of solid tumors in preclinical animal models. Thus, ABT-100 is an attractive candidate for further clinical evaluation. In addition, our results provide plausible insights to explain the impressive potency and selectivity of ABT-100. Finally, we have demonstrated that ABT-100 significantly suppresses the expression of vascular endothelial growth factor (VEGF) mRNA and secretion of VEGF protein, as well as inhibiting angiogenesis in the animal model.

引用

页码：1059 / 1069

页数：11

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