生物活性Dihexa(PNB-0408)，一種寡肽試劑，是一種具有口服活性，血腦屏障可滲透性的血管緊張素IV類似物。Dihexa高親和力結合肝細胞生長因子(HGF)，Kd值為65pM，并增強了其對受體c-Met的活性。Dihexa在動物模型中顯示出優(yōu)異的抗精神病活性以及改善認知功能。Dihexa具有研究阿爾茨海默癥的潛力。靶點Kd:65pM(HGF)體外研究DihexabindswithhighaffinitytoHGFandbothdihexaanditsparentcompoundNorleucine1-AngIVinducec-MetphosphorylationinthepresenceofsubthresholdconcentrationsofHGFandaugmentHGF-dependentcellscattering.Further,dihexaandNle1-AngIVinducehippocampalspinogenesisandsynaptogenesissimilartoHGFitself.DihexaeffectivelyinhibitsHGFdimerizationat1μM.Whiledihexaat1nMand10pMalonedoesnotactivatec-Met,itmarkedlyaugmentsthecapacityofHGFat1.25and2.5ng/mLtoactivatec-Met.
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