Inhibition of Son of Sevenless Homologue 1 (SOS1): Promising therapeutic treatment for KRAS-mutant cancers

Eur J Med Chem. 2023 Dec 5:261:115828. doi: 10.1016/j.ejmech.2023.115828.

Tingkai Chen ¹, Xu Tang ¹, Zhenqi Wang ², Feng Feng ³, Chunlei Xu ², Qun Zhao ², Yulan Wu ², Haopeng Sun ⁴, Yao Chen ⁵

Affiliations

1 School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China.
2 School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China.
3 School of Pharmacy, Nanjing Medical University, 211166, Nanjing, People's Republic of China.
4 School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China. Electronic address: [email protected].
5 School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China. Electronic address: [email protected].

PMID: 37778239 DOI: 10.1016/j.ejmech.2023.115828

Abstract

Kristen rat sarcoma (KRAS) is one of the most common oncogenes in human cancers. As a guanine nucleotide exchange factor, Son of Sevenless Homologue 1 (SOS1) represents a potential therapeutic concept for the treatment of KRAS-mutant cancers because of its activation on KRAS and downstream signaling pathways. In this review, we provide a comprehensive overview of the structure, biological function, and regulation of SOS1. We also focus on the recent advances in SOS1 inhibitors and emphasize their binding modes, structure-activity relationships and pharmacological activities. We hope that this publication can provide a comprehensive compendium on the rational design of SOS1 inhibitors.

Keywords

Cancer therapy; KRAS; PROTACs; SOS1 inhibitors; Small molecules.

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