摘要
SOS1(son of sevenless 1)是激活细胞中大鼠肉瘤(rat sarcoma,Ras)蛋白至关重要的鸟嘌呤核苷酸交换因子(guanine nucleotide exchange factors,GEF)。SOS1蛋白由多段结构域组成,这些结构域的功能与Ras及其下游信号通路的表达密切相关。目前已经报道了大量的SOS1抑制剂与一定量的SOS1激动剂,这些分子大部分能有效抑制下游信号通路的表达。其中由德国勃林格英格翰公司研发的化合物BI-1701963(结构未公布)已进入Ⅰ期临床试验。虽然SOS1化合物的开发还不够成熟,但是该类小分子对于“不可成药”靶点Ras而言,是一种可行的替代策略。本文在查阅相关文献的基础上,对SOS1的结构域以及相关通路进行系统描述,并对目前已有的SOS1小分子调节剂的发展情况进行总结,为SOS1小分子调节剂的研发提供参考。
Son of sevenless 1(SOS1)is a vital guanine nucleotide exchange factor(GEF)that activates rat sarcoma(Ras)protein in cells.SOS1 protein contains multiple domains,the functions of which are closely related to the expression of Ras and its downstream signaling pathways.A large number of SOS1 inhibitors and a certain amount of SOS1 agonists have been reported,and these molecules effectively inhibit the expression of downstream signaling pathways.Among them,compound BI-1701963(structure unpublished)developed by Boehringer Ingelheim,Germany,has entered phase I clinical trials.Although the development of SOS1 compounds is premature,this type of small molecule is an available alternative strategy for the“non-drugable”target Ras.Based on the related literature searching,this paper systematically describes the domains and related pathways of SOS1,and summarizes the development of existing small-molecule SOS1 modulators,providing references for the future research.
作者
范懿庆
唐春雷
范为正
FAN Yi-qing;TANG Chun-lei;FAN Wei-zheng(School of Pharmaceutical Science,Jiangnan University,Wuxi 214122,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2022年第11期1072-1079,共8页
Chinese Journal of New Drugs
