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(jié)合肝細(xì)胞生長(zhǎng)因子(HGF),Kd值為65pM,并增強(qiáng)了其對(duì)受體c-Met的活性。Dihexa在動(dòng)物模型中顯示出優(yōu)異的抗精神病活性以及改善認(rèn)知功能。Dihexa具有研究阿爾茨海默癥的潛力。靶點(diǎn)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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