Biochem/physiol Actions
CXCR4 antagonist and CXCR7 agonist that inhibits CXCR4-mediated HIV infection in cultures and ameliorates bleomycin-induced lung injury in vivo.
TC14012 is a highly stable and non-cytotoxic disulfide-bridged peptide with potent CXCR7 agonist and CXCR4 antagonist activity. TC14012 potently inhibits dual-tropic HIV strain 89.6 infection of CXCR4-expressing U87 glioblastoma cells (IC50 = 19.3 nM) and protects MT-4 cells against HIV-induced cytopathogenicity (EC50 = 0.4 nM). TC14012 also exhibits potent CXCR7-agonizing activity (HEK293T β-Arrestin recruitment EC50 = 350 nM; EC50 = 30 nM with CXCL12/SDF-1 and 140 μM with AMD3100). TC14012 (10 mg/kg i.t.) is efficacious in reducing repetitive bleomycin injections-induced collagen deposition and alveolar epithelial damage in a murine model of lung injury in vivo.