noncompetitive antagonism

KN-62 是一种选择性的、可逆的钙调蛋白依赖性蛋白激酶 II (CaMK-II) 抑制剂，直接与 CaMK-II 酶的钙调蛋白结合位点结合，对大鼠脑 CaMK-II 的IC50值为 0.9 μM。它是非竞争性的P2X7受体拮抗剂，IC50约为 15 nM。

GSK812397 is a potent entry inhibitor of X4-tropic strains of HIV-1, as demonstrated in multiple in vitro cellular assays. GSK812397 is a noncompetitive antagonist of the CXCR4 receptor, with GSK812397 producing a concentration-dependent decrease in both an SDF-1-mediated chemotaxis and intracellular calcium release (IC50s were 0.34+ -0.01 nM and 2.41+ -0.50 nM, respectively). GSK812397 is effective against a broad range of X4- and X4R5-utilizing clinical isolates. The potency and efficacy of GSK812397 are dependent on the individual isolate, with complete inhibition of infection observed with 24 of 30 isolates. GSK812397 does not show any detectable in vitro cytotoxicity and was highly selective for CXCR4. GSK812397 shows acceptable pharmacokinetic properties and bioavailability across species. GSK812397 has antiviral activity against a broad range of X4-utilizing strains of HIV-1 via a noncompetitive antagonism of the CXCR4 receptor.