Related Experiment Video

Updated: Mar 7, 2026

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein
07:08

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein

Published on: January 16, 2020

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Discovery of BBO-11818, a Potent and Selective Noncovalent Inhibitor of (ON) and (OFF) KRAS with Activity against

Carlos Stahlhut1, Anna E Maciag2, Kyle A Sullivan1

  • 1BridgeBio Oncology Therapeutics, South San Francisco, California.

Cancer Discovery
|March 6, 2026
PubMed

Insights

A new drug, BBO-11818, targets multiple KRAS mutations (including KRASG12D and KRASG12V) in both active and inactive states. This pan-KRAS inhibitor shows promise for treating cancers driven by various KRAS mutations.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Targeted therapies for KRAS mutants like KRASG12D and KRASG12V are lacking.
  • Existing KRAS inhibitors often target only specific mutations or states.

Purpose of the Study:

  • To discover and characterize a novel pan-KRAS inhibitor targeting multiple KRAS mutations.
  • To evaluate the efficacy of BBO-11818 in preclinical cancer models.

Main Methods:

  • Discovery of BBO-11818, a noncovalent pan-KRAS inhibitor.
  • Biochemical assays to assess binding affinity and selectivity.
  • Cellular assays for MAPK signaling and viability.
  • In vivo xenograft studies and combination therapy experiments.

Main Results:

  • BBO-11818 targets both inactive (OFF) and active (ON) states of multiple KRAS mutants.
  • Demonstrated high-affinity binding and selectivity over NRAS and HRAS.
  • Potently inhibited MAPK signaling and cell viability in KRAS-driven lines.
  • Induced tumor regressions in KRAS-mutant xenografts and showed enhanced efficacy in combination studies.

Conclusions:

  • BBO-11818 is a potent, selective, orally bioavailable pan-KRAS inhibitor.
  • Shows significant preclinical efficacy as monotherapy and in combination therapies.
  • Has entered Phase I clinical trials for various KRAS-mutated cancers.

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