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.