[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [KRAS G12C inhibitors](https://durgical.com/en/pharmacology/classes/kras-g12c-inhibitors/) › Sotorasib

# Sotorasib

## KRAS G12C inhibitors?

KRAS G12C inhibitors

## High alert?

An error with this medicine can cause serious harm: double checks and protocols are used.

The first KRAS G12C inhibitor: it binds the mutant cysteine and locks KRAS «off»; for lung and colorectal cancers with this mutation.

Updated Nov 1, 2026

Also called: AMG 510

## Quick facts

**Group**
[KRAS G12C inhibitors](https://durgical.com/en/pharmacology/classes/kras-g12c-inhibitors/)

**Target**
Mutant KRAS G12C (small GTPase)

**Used for**
Locally advanced · Metastatic colorectal cancer

**Key effects**
Diarrhoea · Fatigue · Musculoskeletal pain

**Monitor**
Test showing KRAS G12C before starting

**ATC**
L01XX73

No doses: the clinician sets them by the current guideline.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Clinical What the labels mean

- Safety Contraindications
- Key interactions
- What is monitored
- Administration and safety
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## Mechanism of action

✂**Mutant KRAS G12C (small GTPase)**Sotorasib

ⓘ The crystal structure shows sotorasib covalently bound to cysteine 12 of human KRAS G12C in its GDP-bound (inactive) state.

**Target in 3D:** Mutant KRAS G12C (small GTPase). PDB structure 6OIM (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/6OIM) · Drag to rotate · pinch to zoom

Sotorasib forms an irreversible covalent bond with the unique cysteine of KRAS G12C, locking the protein in its inactive GDP-bound state and preventing it from being reloaded with GTP. Downstream growth signalling stops. Normal KRAS, which lacks this cysteine, is spared, so off-target activity is minimal.

- G12C mutation leaves KRAS stuck «on» in the tumour
- Sotorasib bonds covalently to cysteine 12
- KRAS is locked in its inactive GDP state
- Growth signalling to the tumour stops

## Indications

- Locally advanced or metastatic non-small cell lung cancer with KRAS G12C after at least one systemic therapy. [Lung cancer →](https://durgical.com/en/conditions/lung-cancer/)
- Metastatic colorectal cancer with KRAS G12C, with panitumumab, after fluoropyrimidine, oxaliplatin and irinotecan chemotherapy. [Colorectal cancer →](https://durgical.com/en/conditions/colorectal-cancer/)

## Adverse effects

### Common

- Diarrhoea, nausea, vomiting
- Fatigue
- Musculoskeletal pain
- Rash, dry skin
- Cough, swelling of the limbs

### Serious (rare, important)

- Hepatotoxicity with raised liver enzymes
- Interstitial lung disease / pneumonitis (rare)
- Severe diarrhoea

## Contraindications

- No absolute contraindications in the label; used with caution in liver disease

## Key interactions

**Proton pump inhibitors and H2 blockers (e.g. omeprazole, famotidine)**
Reduce absorption; combined use is avoided.

**Antacids**
Reduce absorption; doses are separated in time.

**Strong CYP3A4 inducers (e.g. rifampicin)**
Lower sotorasib levels.

## What is monitored

- Test showing KRAS G12C before starting
- Liver tests regularly
- New or worse cough, breathlessness or fever
- Stool frequency and hydration

## Administration and safety

- Oral, once a day at about the same time; a dose vomited is not repeated that day.
- The label describes a way to disperse the tablets in water for people who cannot swallow them.
- Check the patient's acid-reducing medicines before starting.
- Hazardous oral chemotherapy: handled with gloves and kept away from children; caregivers who are pregnant avoid handling it.

## Pregnancy and breastfeeding

Pregnancy is discussed with the doctor and reported at once if it occurs; breastfeeding is avoided during treatment and for a short time after.

## Nursing care

- Review liver tests before refills and report jaundice, dark urine or right upper abdominal pain.
- Ask about cough, breathlessness and fever.
- Check for diarrhoea and dehydration.
- Teaching: do not start antacids or heartburn medicines without asking; take it at the same time each day.

## Pharmacokinetics

**Absorption**
Oral, with or without food; absorption falls with acid-reducing drugs.

**Metabolism**
Non-enzymatic conjugation and CYP3A.

**Half-life**
Short, about 5 hours.

## Memory aid

«SOTO grabs the C»: sotorasib clamps Cysteine 12 of KRAS G12C and switches it off; keep stomach acid normal so it is absorbed.

## Test yourself

Think of the answer, then tap the question to see it.

## Which mutation must a tumour have to be treated with sotorasib?

KRAS G12C.

## How does sotorasib bind its target?

Covalently and irreversibly to cysteine 12, locking KRAS in the inactive GDP-bound state.

## Why are proton pump inhibitors avoided with sotorasib?

They reduce stomach acid and therefore sotorasib absorption.

## Which antibody is combined with sotorasib in colorectal cancer?

Panitumumab, an anti-EGFR antibody.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/sotorasib/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## What the labels mean

**High alert**
An error with this medicine can cause serious harm: double checks and protocols are used.

## Connections

## Related drugs 3

- [Adagrasib](https://durgical.com/en/pharmacology/adagrasib/)
- [Omeprazole](https://durgical.com/en/pharmacology/omeprazole/)
- [Famotidine](https://durgical.com/en/pharmacology/famotidine/)

## Related conditions 2

- [Lung cancer](https://durgical.com/en/conditions/lung-cancer/)
- [Colorectal cancer](https://durgical.com/en/conditions/colorectal-cancer/)

[← Back to the class: KRAS G12C inhibitors](https://durgical.com/en/pharmacology/classes/kras-g12c-inhibitors/)

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); [Sotorasib - NCI](https://www.cancer.gov/about-cancer/treatment/drugs/sotorasib) (National Cancer Institute, 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L01XX73) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/pharmacology/sotorasib/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/sotorasib/