Rab7 inhibitor

A Rab7 inhibitor is a pharmacological agent designed to block the activity of the Rab7 GTPase, a critical regulator of late endosomal trafficking, lysosomal biogenesis, and autophagy within the Ras superfamily of small GTPases. The most prominent representative of this class is ML282 (also known as CID 1067700), which was identified as the first-in-class competitive nucleotide-binding inhibitor of Rab GTPases. ML282 binds to the GTP/GDP binding pocket of Rab7 with nanomolar potency (Ki of 13-19 nM), effectively preventing its conformational activation and interaction with downstream effectors. While it exhibits some pan-inhibitory activity across the Ras superfamily, it shows significant efficacy toward Rab7. Preclinical research has demonstrated that Rab7 inhibition can arrest tumor cell growth in B-cell lymphomas (particularly diffuse large B-cell lymphoma), reduce autoantibody responses in systemic lupus erythematosus (SLE), and impair the maintenance of colorectal cancer stem cells. Currently, these agents are primarily utilized as chemical probes in research settings to study endolysosomal signaling and have not yet entered clinical development.

Other names

2-(benzoylcarbamothioylamino)-5,5-dimethyl-4,7-dihydrothieno[2,3-c]pyran-3-carboxylic acidRab7 GTPase inhibitorRab-7 GTPase inhibitorRab 7 GTPase inhibitor