These new molecules bind to Ras proteins with very high strength—on the nanomolar scale—similar to or better than existing drugs designed to target a specific KRas mutation, but potentially effective against many more mutations.
Evidence from Studies
No evidence studies found yet.
What Would Prove This
Per GRADE and EBM methodology, here is what ideal scientific evidence would look like to definitively prove or disprove this claim, ordered from strongest to weakest.
Whether nanomolar binding affinity of Ras inhibitors correlates with clinical efficacy across different compounds and mutation types.
A systematic review and meta-analysis of all published Ras inhibitors with reported biochemical Kd values and clinical trial outcomes, correlating binding affinity with objective response rate and progression-free survival across mutation subtypes.
Whether a Ras inhibitor with nanomolar affinity improves survival compared to a lower-affinity compound in patients with KRas-mutant cancers.
A double-blind, randomized phase II trial of 120 patients with KRas-mutant cancers, comparing a high-affinity (Kd < 10 nM) inhibitor to a lower-affinity (Kd > 100 nM) analog, with primary endpoint of progression-free survival and mandatory pharmacodynamic assessment of target engagement.
Whether patients receiving inhibitors with higher nanomolar affinity show greater tumor shrinkage than those receiving lower-affinity compounds.
A prospective cohort study of 150 patients with KRas-mutant cancers receiving various Ras inhibitors with known Kd values, correlating pre-treatment Kd with tumor response by RECIST 1.1 over 24 weeks.
Whether responders to Ras inhibitors have tumors with higher target affinity than non-responders.
A matched case-control study comparing 50 responders to 50 non-responders to Ras inhibitors, measuring binding affinity of the drug to Ras protein extracted from tumor biopsies using surface plasmon resonance.
Whether the binding affinity of the inhibitor correlates with its potency in inhibiting Ras-Raf interaction in cell lysates.
A cross-sectional analysis of 30 purified Ras proteins from different cell lines, measuring inhibitor binding affinity (Kd) by SPR and Ras-Raf inhibition (IC50) in biochemical assays, correlating the two values.