Bexotegrast

Bexotegrast (PLN-74809) is an orally active, potent dual αvβ6/αvβ1 integrin inhibitor with K_d of 5.7 nM and 3.4 nM, respectively. Bexotegrast inhibits αvβ6- and αvβ1-induced TGF-β activation with IC₅₀ values of 29.8 nM and 19.2 nM, respectively. Bexotegrast has antifibrogenic effects and block multiple avenues of TGF-β activation in the fibrotic lung^[1][2]. In Vitro:Bexotegrast (PLN-74809; 1.82 µM; 7-day incubation) significantly reduces collagen type I alpha I (COL1A1) mRNA expression by 54% in precision-cut lung slices (PCLSs). PLN-74809 shows an approximately 50% reduction in Smad2 phosphorylation^[2].
Bexotegrast (1.82 µM; 3-day incubation) dose-dependently reduces Col1a1 mRNA expression in PCLSs prepared from fibrotic mouse lungs by up to 71%^[2].
Bexotegrast fully inhibits αvβ6 integrin-mediated adhesion to LAP by normal human bronchial epithelial cells with an IC₅₀ of 39.3 nM^[2].
In Vivo:Bexotegrast (PLN-74809; orally; 100, 250, and 500 mg/kg twice daily; from Day 7 to Day 21) shows a dose-dependent, significant reduction in interstitial fibrillar collagen deposition in Bleomycin-challenged mice. Bexotegrast dose-dependently blocks Smad3 phosphorylation^[2].