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Updated: Sep 19, 2025

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Analysis of Pan-Specific Inhibitors of Oncogenic Mutant Forms of KRAS GTPase

Ilya A Eliseev1, Dmitrii O Shkil2, Valentina S Shumakova1

  • 1Medicinal Biotechnology Department, Sirius University of Science and Technology, Olimpiyskiy ave. 1, Sirius, Krasnodar Region, 354340, Russia.

Current Medicinal Chemistry
|June 17, 2025
PubMed

Insights

New pan-KRAS inhibitors offer broader cancer treatment options beyond specific mutations like KRASG12C. These novel compounds target multiple KRAS forms, potentially increasing patient benefit and reducing drug resistance.

Area of Science:

  • Oncology
  • Medicinal Chemistry
  • Drug Discovery

Background:

  • KRAS protein is a critical target in cancer therapy.
  • Current covalent KRAS inhibitors (e.g., sotorasib, adagrasib) are limited to KRASG12C mutations and face resistance issues.
  • Pan-KRAS inhibitors represent a new class targeting multiple KRAS mutations.

Purpose of the Study:

  • To review recent patents (2022-2024) on novel pan-specific KRAS inhibitors.
  • To identify structural features of active pan-KRAS inhibitors.
  • To assess the potential of pan-KRAS inhibitors in cancer therapy.

Main Methods:

  • Patent literature review (2022-2024).
  • Analysis of molecular structures and activity data from 28 patents.
  • Structure-activity relationship (SAR) analysis.

Main Results:

  • Identified novel pan-specific KRAS inhibitors described in recent patents.
  • Evaluated the activity and selectivity of various compound examples.
  • Determined key structural features associated with high activity in pan-KRAS inhibitors.

Conclusions:

  • Pan-KRAS inhibitors show promise for broader application in KRAS-mediated cancers.
  • Targeting multiple KRAS mutations may overcome limitations of current therapies and reduce resistance.
  • This review highlights promising structural motifs for future pan-KRAS inhibitor development.
Keywords:
BI-2865.CancerKRASKRAS-G12X/G13D/Q61HRASSAR analysisdrug developmentmutationspan-KRAS inhibitorspatents

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