An updated patent review of SOS1 inhibitors (2022-present).

Abstract

Introduction: SOS1 is a crucial guanine nucleotide exchange factor for KRAS. It facilitates the transition of KRAS from inactive GDP-bound state to active GTP-bound state. The activation of KRAS triggers downstream signaling pathways, promoting tumor initiation and progression. Inhibiting SOS1 to prevent KRAS activation is an effective strategy for treating tumors driven by KRAS.

Areas covered: This review identified patents claiming to be SOS1 inhibitors or SOS1-KRAS interaction modulators published between January 2022 and June 2024 using Cortellis Drug Discovery Intelligence. A total of 15 patent applications from 5 different applicants were assessed.

Expert opinions: In KRAS-driven tumors, inhibiting SOS1 significantly affect cell proliferation and migration by modulating the RAS/MAPK and PI3K/AKT/mTOR signaling pathways. Since 2022, numerous patents for SOS1 inhibitors have been published. The majority of SOS1 inhibitors are currently in the preclinical phase of development, with only a few progressing to clinical trials. However, these inhibitors face significant challenges in clinical studies, including limited efficacy of monotherapies, safety concerns, and the necessity to enhance PK properties. Despite their excellent in vitro performance, SOS1 inhibitors must address issues related to safety, pharmacokinetics, and pharmacodynamics in clinical applications.