CWHM-12

CWHM-12 is a small-molecule RGD peptidomimetic antagonist that functions as a pan–αV integrin inhibitor—targeting multiple integrin subtypes.

• It exhibits potent inhibitory activity toward:

  • αvβ8 (IC₅₀ ≈ 0.2 nM)

  • αvβ3 (≈ 0.8 nM)

  • αvβ6 (≈ 1.5 nM)

  • αvβ1 (≈ 1.8 nM)

  • Displays much lower potency toward αvβ5 (≈ 61 nM) and negligible activity against non-αV integrins like αIIbβ3 or α2β1 (IC₅₀ > 5000 nM)

Structural Insight: The compound mimics the Arg-Gly-Asp (RGD) motif—the key integrin-binding sequence—via a cyclic guanidino-substituted phenyl (Arg mimetic) linked to a phenyl-substituted β-amino acid (Asp mimetic), with glycine as the connector IUPHAR/BPS Guide to PharmacologyNature

Biological Effects & Applications

1. Anti-Fibrotic Activity

• In vivo models demonstrate robust reduction of fibrosis in liver, lung, skeletal, and cardiac tissues—even post-establishment of disease.

• Mechanistically, CWHM-12 inhibits αV integrin–mediated activation of TGF-β, culminating in decreased phosphorylation of SMAD3 and collagen expression IUPHAR/BPS Guide to Pharmacology

2. Modulation of Hepatic Stellate Cell (HSC) Activation

• In liver fibrosis models, CWHM-12 suppresses the activity and proliferation of activated HSCs.

• It does so by promoting the Hippo signaling pathway, which inhibits YAP nuclear translocation, leading to apoptosis and G₁ arrest in these cells SynapseScienceDirect.

3. Host Response in Tuberculosis (TB)

• In a mouse model of Mycobacterium tuberculosis infection, early CWHM-12 treatment improved disease outcomes.

• This is potentially due to suppression of TGF-β–mediated inflammation, resulting in reduced expression of inflammatory markers (iNOS, MIP-2, IL-10) and better infection control PubMed.

0°C (short term), -20°C (long term), desiccated