详情页 - 四川省肿瘤医院知识库

当前位置：首页 > 详情页

Current advances and development strategies of targeting son of sevenless 1 (SOS1) in drug discovery

文献详情

资源类型：

Pubmed体系：

作者：

机构： [1]Department of Neurology, Neuro-system and Multimorbidity Laboratory and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [2]Department of Pulmonary and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [3]Department of Dermatology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

出处：

DOI：

ISSN：

关键词： SOS1 RAS Inhibitor Activator Drug discovery

摘要：

The Son of Sevenless 1 (SOS1) guanine nucleotide exchange factor, prevalent across eukaryotic species, plays a pivotal role in facilitating the attachment of RAS protein to GTP, thereby regulating the activation of intracellular RAS proteins. This regulation is part of a feedback mechanism involving SOS1, which allows both activators and inhibitors of SOS1 to exert control over downstream signaling pathways, demonstrating potential anti-tumor effects. Predominantly, small molecule modulators that target SOS1 focus on a hydrophobic pocket within the CDC25 protein domain. The effectiveness of these modulators largely depends on their ability to interact with specific amino acids, notably Phe890 and Tyr884. This interaction is crucial for influencing the protein-protein interaction (PPI) between RAS and the catalytic domain of SOS1. Currently, most small molecule modulators targeting SOS1 are in the preclinical research phase, with a few advancing to clinical trials. This progression raises safety concerns, making the assurance of drug safety a primary consideration alongside the enhancement of efficacy in the development of SOS1 modulators. This review encapsulates recent advancements in the chemical categorization of SOS1 inhibitors and activators. It delves into the evolution of small molecule modulation targeting SOS1 and offers perspectives on the design of future generations of selective SOS1 small molecule modulators.Copyright © 2024 Elsevier Masson SAS. All rights reserved.

基金：

语种：

PubmedID：

中科院(CAS)分区：

出版当年[2024]版：

无

最新[2023]版：

大类 | 2 区

医学

小类 | 1 区药物化学

第一作者：

第一作者机构： [1]Department of Neurology, Neuro-system and Multimorbidity Laboratory and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [2]Department of Pulmonary and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

共同第一作者：

通讯作者：

推荐引用方式(GB/T 7714)：

APA：

MLA：

相关文献

[1]Structures of a diverse set of colchicine binding site inhibitors in complex with tubulin provide a rationale for drug discovery. [2]In silico identification of potent small molecule inhibitors targeting epidermal growth factor receptor 1 [3]Advances of Osteosarcoma Models for Drug Discovery and Precision Medicine [4]Artificial intelligence in cancer target identification and drug discovery. [5]Targeting ferroptosis: Paving new roads for drug design and discovery [6]Nuclear Receptors: Recent Drug Discovery for Cancer Therapies. [7]Discovery of a drug to treat airway mucus hypersecretion [8]Systems biology approaches based discovery of a small molecule inhibitor targeting both c-Met/PARP-1 and inducing cell death in breast cancer [9]Simultaneous 2D and 3D cell culture array for multicellular geometry, drug discovery and tumor microenvironment reconstruction. [10]Current progress and novel strategies that target CDK12 for drug discovery