Related Experiment Video

Updated: Nov 9, 2025

Generation of Murine Cardiac Pacemaker Cell Aggregates Based on ES-Cell-Programming in Combination with Myh6-Promoter-Selection
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Generation of Murine Cardiac Pacemaker Cell Aggregates Based on ES-Cell-Programming in Combination with Myh6-Promoter-Selection

Published on: February 17, 2015

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Targeting Son of Sevenless 1: The pacemaker of KRAS

Dirk Kessler1, Daniel Gerlach1, Norbert Kraut1

  • 1Discovery Research, Boehringer Ingelheim Regional Center Vienna GmbH & Co KG, 1120, Vienna, Austria.

Current Opinion in Chemical Biology
|April 13, 2021
PubMed

Insights

Son of Sevenless (SOS) protein regulates KRAS, a key cancer driver. New SOS1 inhibitors show promise for treating KRAS-mutated cancers and RASopathies, with one now in clinical trials.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Son of Sevenless (SOS) is a guanine nucleotide exchange factor crucial for KRAS signaling.
  • Activating SOS1 mutations are linked to Noonan syndrome, and KRAS alterations drive numerous cancers.
  • While KRASG12C inhibitors show efficacy, most KRAS mutations remain untargeted.

Purpose of the Study:

  • To review the function of SOS1 in cell signaling.
  • To discuss the role of SOS1 and KRAS in cancer and RASopathies.
  • To provide an overview of SOS1 inhibitors and their therapeutic potential.

Main Methods:

  • Literature review of SOS1 function, activators, and inhibitors.
  • Analysis of SOS1's role in KRAS activation and its implications in disease.
  • Discussion of emerging SOS1-targeted therapies.

Main Results:

  • SOS1 inhibition demonstrates antiproliferative effects across various KRAS mutants.
  • Discovery of druggable pockets on SOS1 has led to potent inhibitors like BI-3406.
  • The first SOS1 inhibitor has advanced to clinical trials for KRAS-mutated cancers.

Conclusions:

  • SOS1 is a critical regulator of KRAS and a promising therapeutic target.
  • Targeting SOS1 offers a potential strategy for treating a broad spectrum of KRAS-driven cancers.
  • Further research into SOS1 inhibitors may unlock new treatments for RASopathies and cancers.
Keywords:
CancerKRASMedicinal chemistryProtein–protein interactionRASopathiesSOS1

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