BIRT 377

BIRT 377 is a negative allosteric modulator (NAM) of lymphocyte function-associated antigen-1 (LFA-1). It binds to LFA-1 at a site distal to residues involved in intercellular adhesion molecule interactions and induces a conformational change to its inactive state. BIRT 377 selectively inhibits the interaction of LFA-1 to intercellular adhesion molecule-1 (ICAM-1) over the interaction between ITGAM/CD11b, also known as Mac-1, and ICAM-1 in cell-free assays at 225 µM. It inhibits LFA-1-mediated binding of SKW-3 cells to ICAM-1 (IC50 = 2. µM) and reduces plasma IL-2 levels increased by staphylococcal enterotoxin B (SEB) in mice when administered at doses of 25 and 50 mg/kg. Intrathecal administration of BIRT 377 (500 ng/animal) reduces allodynia in prenatal alcohol exposed (PAE) rats in a model of sciatic neuropathy induced by a minor chronic constriction injury.. Solulibility: DMSO: Soluble: = 10 mg/ml: Ethanol: Slightly soluble: 0.1-1 mg/ml.