AMG-548-dihydrochloride-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAMG-548dihydrochlorideCat.No.:HY-108642B分⼦式:C₂₉H₂₉Cl₂N₅O分⼦量:534.48作⽤靶点:p38MAPK;CaseinKinase作⽤通路:MAPK/ERKPathway;CellCycle/DNADamage;StemCell/Wnt储存⽅式:-20°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:10mg/mL(18.71mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.8710mL9.3549mL18.7098mL5mM0.3742mL1.8710mL3.7420mL10mM0.1871mL0.9355mL1.8710mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1mg/mL(1.87mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1mg/mL(1.87mM);Clearsolution1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性AMG-548dihydrochloride⼀种⼝服有效的，选择性p38α抑制剂(Ki=0.5nM)，对p38β略有选择性(Ki=36nM)并且对p38γ和p38δ具有>1000倍的选择性。AMG-548dihydrochloride也有效抑制全⾎LPS刺激的TNFα(IC50=3nM)。AMG-548dihydrochloride通过直接抑制酪蛋⽩激酶1(Caseinkinase1)同种型δ和ε来抑制Wnt信号传导。IC50&Targetp38αp38βp38δp38γ0.5nM(Ki)3.6nM(Ki)2600nM(Ki)4100nM(Ki)dogp38αJNK1JNK2JNK35.0nM(Ki)11480nM(Ki)39nM(Ki)61nM(Ki)CK1体外研究AMG-548dihydrochlorideshows>1000foldselectiveagainstp38γ(Ki=2600nM)andp38δ(ki=4100nM).AMG-548dihydrochloridehasanmodestselectivityagainstJNK2(ki=39nM)andJNK3(ki=61nM).AMG-548dihydrochlorideisalsoextremelypotentintheinhibitionofwholebloodLPSstimulatedTNFa(IC50=3nM)andIL1b(IC50=7nM)aswellasTNFainducedIL-8(IC50=0.7nM)andIL-1binducedIL-6(IC5050=1.3nM)inhumanwholeblood[1].AMG-548dihydrochloride(10μM)inhibitsthehDvl2shift[2].体内研究AMG-548dihydrochloridehasratFof62%anddogFof47%.Thet1/2is4.6hoursinratsand7.3hoursindogs[1].REFERENCES[1].LeeMR,etal.MAPkinasep38inhibitors:clinicalresultsandanintimatelookattheirinteractionswithp38alphaprotein.CurrMedChem.2005;12(25):2979-94.[2].VerkaarF,etal.InhibitionofWnt/β-cateninsignalingbyp38MAPkinaseinhibitorsisexplainedbycross-reactivitywithcaseinkinaseIδ/ɛ.ChemBiol.2011Apr22;18(4):485-94.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplicati