生物活性

• 描述CD11b/CD18 is a dimeric integrin highly expressed on the surface of myeloid cells and plays an important role in transendothelial migration and tissue recruitment during inflammatory immune responses. ADH-503 is a small-molecule allosteric agonist of CD11b/CD18 that partially actives CD11b conformation through binding. It increased CD11b/CD18-dependent cell adhesion to fibrinogen with an EC50 value of 4mM. Treatment of leukocytes with 15μM ADH-503 led to a significant decrease in lateral migration and migration velocity compared to DMSO-treated controls. The intravital microscopic analysis of mouse cremaster muscle showed that ADH-503 at 100μM decreased the rolling velocity of leukocytes in TNF-α-treated venules. In a mouse model of acute, thioglycolate-induced peritonitis, administration of ADH-503 (200μL of a 50μM solution in saline) 30 min before thioglycolate injection reduced the amount of neutrophil accumulation by 40% compared to vehicle-pretreated mice. Also, neutrophil accumulation in ADH-503-treated mice was reduced at 4 h after thioglycolate injection and stayed reduced at 12 h^[1].
• 作用机制ADH-503 is a small-molecule agonist of CD11b/CD18 that preferentially binds to the open conformation of the αA domain in CD11b/CD18, thereby allosterically stabilizing the αA domain in its high-affinity conformation and activating CD11b/CD18^[1].