AMG-548-dihydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAMG-548dihydrochlorideCat.No.:HY-108642B分?式:C??H??Cl?N?O分?量:534.48作?靶點(diǎn):p38MAPK;CaseinKinase作?通路:MAPK/ERKPathway;CellCycle/DNADamage;StemCell/Wnt儲(chǔ)存?式:-20°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:10mg/mL(18.71mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.8710mL9.3549mL18.7098mL5mM0.3742mL1.8710mL3.7420mL10mM0.1871mL0.9355mL1.8710mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1mg/mL(1.87mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1mg/mL(1.87mM);Clearsolution1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性AMG-548dihydrochloride?種?服有效的，選擇性p38α抑制劑(Ki=0.5nM)，對(duì)p38β略有選擇性(Ki=36nM)并且對(duì)p38γ和p38δ具有>1000倍的選擇性。AMG-548dihydrochloride也有效抑制全?LPS刺激的TNFα(IC50=3nM)。AMG-548dihydrochloride通過(guò)直接抑制酪蛋?激酶1(Caseinkinase1)同種型δ和ε來(lái)抑制Wnt信號(hào)傳導(dǎo)。IC50&Targetp38αp38βp38δp38γ0.5nM(Ki)3.6nM(Ki)2600nM(Ki)4100nM(Ki)dogp38αJNK1JNK2JNK35.0nM(Ki)11480nM(Ki)39nM(Ki)61nM(Ki)CK1體外研究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].體內(nèi)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/?.ChemBiol.2011Apr22;18(4):485-94.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplicati