GSK3335103 (GSK-3335103) is a potent, oral, small molecule RGD-mimetic αvβ6 integrin inhibitor with pKi of 9.96.
GSK3335103 was shown to have a minimum of 4-fold (αvβ3) and a maximum >91,201 (αIIbβ3) selectivity over the other RGD integrins.
GSK3335103 caused a concentration-dependent internalisation of αvβ6 in NHBE cells with a pEC50 of 9.35.
Treatment with GSK3335103 resulted in a concentration-dependent reduction in pSmad2 signalling in NHBE cells with a pIC50 value of 8.19, also inhibited pSmad2 signalling in a concentration-dependent manner with a comparable potency in an ex vivo IPF PCLS system.
GSK3335103 inhibit the activation of TGFβ in a murine model of bleomycin-induced lung fibrosis, as measured by αvβ6 engagement, TGFβ signalling and collagen deposition, with a prolonged duration of action observed in vivo.
