KRAS G12C inhibitors
Oral drugs that lock the mutant KRAS G12C protein in its «off» state; used in lung and colorectal cancers that carry this mutation.
What they are
KRAS is one of the most frequently mutated oncogenes, and for decades it was considered undruggable. The G12C mutation replaces glycine 12 with a cysteine, creating a handle that sotorasib and adagrasib grab covalently. A test of the tumour must show KRAS G12C before treatment.
Mechanism of action
The drugs bind covalently and irreversibly to cysteine 12 only when KRAS is in its inactive GDP-bound form. KRAS can no longer be reloaded with GTP, and the RAF-MEK-ERK growth signal stops. Normal (wild-type) KRAS, which has no cysteine there, is spared.
Target: Mutant KRAS G12C (small GTPase)
Drugs in this class
- SotorasibThe first KRAS G12C inhibitor: it binds the mutant cysteine and locks KRAS «off»; for lung and colorectal cancers with…Mutant KRAS G12C (small GTPase)
- AdagrasibOral covalent KRAS G12C inhibitor for lung cancer and, with cetuximab, colorectal cancer. Watch the liver, the lungs…Mutant KRAS G12C (small GTPase)
Test yourself
Think of the answer, then tap the question to see it.
Why can KRAS G12C be targeted but not most other KRAS mutants?
The mutant cysteine at position 12 gives the drug a residue to bind covalently.
In which state of KRAS do these drugs bind?
The inactive, GDP-bound state, which they lock in place.
What partner drug is used with KRAS G12C inhibitors in colorectal cancer?
An anti-EGFR antibody: panitumumab with sotorasib or cetuximab with adagrasib.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Sotorasib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Adagrasib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.