生物活性Dihexa(PNB-0408),一种寡肽试剂,是一种具有口服活性,血脑屏障可渗透性的血管紧张素IV类似物。Dihexa高亲和力结合肝细胞生长因子(HGF),Kd值为65pM,并增强了其对受体c-Met的活性。Dihexa在动物模型中显示出优异的抗精神病活性以及改善认知功能。Dihexa具有研究阿尔茨海默症的潜力。靶点Kd:65pM(HGF)体外研究DihexabindswithhighaffinitytoHGFandbothdihexaanditsparentcompoundNorleucine1-AngIVinducec-MetphosphorylationinthepresenceofsubthresholdconcentrationsofHGFandaugmentHGF-dependentcellscattering.Further,dihexaandNle1-AngIVinducehippocampalspinogenesisandsynaptogenesissimilartoHGFitself.DihexaeffectivelyinhibitsHGFdimerizationat1μM.Whiledihexaat1nMand10pMalonedoesnotactivatec-Met,itmarkedlyaugmentsthecapacityofHGFat1.25and2.5ng/mLtoactivatec-Met.
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