**Background**
Integrins are heterodimeric transmembrane receptors that mediate cell-extracellular matrix (ECM) adhesion and signal transduction, playing critical roles in various physiological and pathological processes. Among the integrin family, αvβ1 integrin is particularly involved in the regulation of tissue remodeling and the progression of fibrosis. Pathological activation of this integrin is often associated with the accumulation of ECM components, leading to organ dysfunction in conditions such as liver and lung fibrosis. Consequently, the development of highly selective inhibitors targeting αvβ1 integrin has become a significant focus for therapeutic intervention in fibrotic diseases. In this context, we will introduce a potent and selective inhibitor – αvβ1 integrin-IN-1.
**Definition**
αvβ1 integrin-IN-1 (also known as Compound C8) is a potent and selective αvβ1 integrin inhibitor with an IC50 value of 0.63 nM.
**In Vitro and In Vivo Studies**
Based on the αvβ1 integrin-IN-1 technical information, this compound utilizes an N-arylsulfonyl-l-proline scaffold to achieve high potency and selectivity. In αvβ1 integrin-IN-1 in vitro assays, the compound demonstrated significant inhibition of αvβ1 integrin-mediated CHO cell adhesion to fibronectin (IC50 = 0.63 nM) following a preincubation period of 15 to 30 minutes and a 60-minute adhesion incubation, as measured by crystal violet staining. Notably, αvβ1 integrin-IN-1 exhibits exceptional selectivity; it showed negligible inhibitory activity (IC50 > 10,000 nM) against other integrins, including αvβ8-mediated SNB-19 cell adhesion to TGFβ1 LAP, α5β1-mediated SW480 cell adhesion to fibronectin, αvβ3-mediated SW480 cell adhesion to fibrinogen, and wild-type αvβ5-mediated SW480 cell adhesion to vitronectin. Regarding αvβ1 integrin-IN-1 in vivo applications, the compound has demonstrated significant antifibrotic effects by reducing fibrotic markers in mouse models of both liver and lung fibrosis. In conclusion, αvβ1 integrin-IN-1 is a highly selective and potent αvβ1 integrin inhibitor that holds promise for the treatment of fibrotic diseases.
Keywords
αvβ1 integrin-IN-1, 1689540-62-2, Integrin, αvβ1, Antifibrotic, Fibrosis, Inhibitor, inhibitor, inhibit
References