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# 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.

Updated Nov 1, 2026

## 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)

## Key points

- Only for tumours with the KRAS G12C mutation, confirmed by testing.
- In colorectal cancer they are combined with an anti-EGFR antibody (sotorasib with panitumumab, adagrasib with cetuximab).
- Diarrhoea, nausea and liver enzyme rises are typical; pneumonitis is rare but serious.
- Adagrasib can prolong the QT interval; sotorasib absorption falls with acid-reducing drugs.

## Drugs in this class

- [**Sotorasib** The first KRAS G12C inhibitor: it binds the mutant cysteine and locks KRAS «off»; for lung and colorectal cancers with… Mutant KRAS G12C (small GTPase)](https://durgical.com/en/pharmacology/sotorasib/)
- [**Adagrasib** Oral covalent KRAS G12C inhibitor for lung cancer and, with cetuximab, colorectal cancer. Watch the liver, the lungs… Mutant KRAS G12C (small GTPase)](https://durgical.com/en/pharmacology/adagrasib/)

## 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.

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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](https://medlineplus.gov/druginfo/meds/a621036.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [Adagrasib: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a623003.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L01XX) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/kras-g12c-inhibitors/