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This research aims to design and synthesize effective KRAS degraders for treating cancers with specific KRAS mutations.

CRBN-Based Pan-KRAS Degraders Targeting KRAS G12 Mutations in Cancer

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This research aims to design and synthesize effective KRAS degraders for treating cancers with specific KRAS mutations.
Synthesis of CRBN-based PROTACs targeting G12D, G12V, and G12C KRAS mutations.
In vitro efficacy assays measuring DC50 and IC50 in mutated cell lines.
Evaluation of pharmacokinetic properties in animal models including mice, rats, dogs, and monkeys.
Assessment of tumor growth inhibition in xenograft models at specified dosages.
Achieved less than 1 nM DC50 and IC50 in mutated cell lines.
Demonstrated over 92% tumor growth inhibition in SW620 xenograft models.
Reported over 90% tumor regression in SW1990 xenograft models at 10 mg/kg dose.

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This research develops CRBN-based PROTACs to effectively target KRAS G12 mutations, indicating potential for improved cancer treatment.

Wang et al. (2026) studied this question.

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