Orally available Colivin traps TRPV3 in an inactive state and suppresses intestinal inflammation.

Orally available Colivin traps TRPV3 in an inactive state, effectively suppressing intestinal inflammation and ulcerative colitis in mice with enhanced stability.

• Why it matters: TRPV3's role in intestinal health is not well understood, and existing inhibitors like KM-001 have limited therapeutic potential due to poor metabolic stability, creating a need for more effective treatments.
• What they did: Researchers developed Colivin, a derivative of KM-001, with improved stability and oral bioavailability, and used cryo-EM and mutagenesis to reveal its binding to TRPV3's vanilloid pocket, stabilizing inactive conformations.
• The result: Oral Colivin significantly reduced colitis symptoms in wild-type mice, demonstrating its potential as a targeted therapy for inflammatory bowel diseases and guiding future design of selective TRPV3 inhibitors.