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ABCB1 limits brain exposure of the KRAS G12C inhibitor sotorasib, whereas ABCB1, CYP3A, and possibly OATP1a/1b restrict its oral availability - PubMed

ABCB1 limits brain exposure of the KRAS G12C inhibitor sotorasib, whereas ABCB1, CYP3A, and possibly OATP1a/1b restrict its oral availability - PubMed

Source : https://pubmed.ncbi.nlm.nih.gov/35192958/

Sotorasib (Lumakras TM ) is the first FDA-approved KRAS G12C inhibitor for treatment of patients with non-small cell lung cancer (NSCLC) carrying this mutation. Using genetically modified mouse models, we studied the influence of the efflux transporters ABCB1 and ABCG2, the OATP1a ...


Conclusion/Relevance: Collectively, the oral availability of sotorasib was markedly limited by CYP3A and possibly also by ABCB1 and OATP1a/b, whereas its brain accumulation was strongly restricted by ABCB1. The obtained results may help to further optimize the safety and efficacy of sotorasib in clinical use.