The Department of Pharmaceutical Sciences & Experimental Therapeutics, University of Iowa, College of Pharmacy, Iowa City, IA, USA.
Future Med Chem. 2013 Jun;5(9):995-1007. doi: 10.4155/fmc.13.91.
Ligands for G-protein-coupled receptors (GPCRs) represent approximately 50% of currently marketed drugs. RGS proteins modulate heterotrimeric G proteins and, thus, GPCR signaling, by accelerating the intrinsic GTPase activity of the Gα subunit. Given the prevalence of GPCR targeted therapeutics and the role RGS proteins play in G protein signaling, some RGS proteins are emerging as targets in their own right. One such RGS protein is RGS17. Increased RGS17 expression in some prostate and lung cancers has been demonstrated to support cancer progression, while reduced expression of RGS17 can lead to development of chemotherapeutic resistance in ovarian cancer. High-throughput screening is a powerful tool for lead compound identification, and utilization of high-throughput technologies has led to the discovery of several RGS inhibitors, thus far. As screening technologies advance, the identification of novel lead compounds the subsequent development of targeted therapeutics appears promising.
G 蛋白偶联受体 (GPCR) 的配体约占目前上市药物的 50%。RGS 蛋白通过加速 Gα 亚基的内在 GTP 酶活性来调节异三聚体 G 蛋白和 GPCR 信号转导。鉴于 GPCR 靶向治疗药物的普遍性以及 RGS 蛋白在 G 蛋白信号转导中的作用，一些 RGS 蛋白本身正成为新的靶点。其中一种 RGS 蛋白是 RGS17。已经证明，一些前列腺癌和肺癌中 RGS17 的表达增加有助于癌症的进展，而 RGS17 的表达减少会导致卵巢癌对化疗药物产生耐药性。高通量筛选是一种强大的先导化合物鉴定工具，迄今为止，利用高通量技术已经发现了几种 RGS 抑制剂。随着筛选技术的进步，新型先导化合物的鉴定和靶向治疗药物的开发似乎很有希望。
