TPC2-A1-N-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrariesTPC2-A1-NCat.No.:HY-131614CASNo.:136186-07-7分?式:C??H?Cl?F?N?O?分?量:401.17作?靶點(diǎn):CalciumChannel作?通路:MembraneTransporter/IonChannel;NeuronalSignaling儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:250mg/mL(623.18mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.4927mL12.4635mL24.9271mL5mM0.4985mL2.4927mL4.9854mL10mM0.2493mL1.2464mL2.4927mL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，并請(qǐng)注意儲(chǔ)備液的保存?式和期限。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%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.08mg/mL(5.18mM);Clearsolution此?案可獲得≥2.08mg/mL(5.18mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL20.8mg/mL的澄DMSO儲(chǔ)備液加到400μLPEG300中，混合均勻；向上述2.體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。請(qǐng)依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(5.18mM);Clearsolution1/3此?案可獲得≥2.08mg/mL(5.18mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL20.8mg/mL的澄DMSO儲(chǔ)備液加到900μL20%的SBE-β-CD?理鹽??溶3.液中，混合均勻。請(qǐng)依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥2.08mg/mL(5.18mM);Clearsolution此?案可獲得≥2.08mg/mL(5.18mM，飽和度未知)的澄溶液，此?案不適?于實(shí)驗(yàn)周期在半個(gè)?以上的實(shí)驗(yàn)。以1mL?作液為例，取100μL20.8mg/mL的澄DMSO儲(chǔ)備液加到900μL??油中，混合均勻。BIOLOGICALACTIVITY?物活性TPC2-A1-N?種強(qiáng)?的Ca2+-可滲透雙孔通道2(TPC2)的激動(dòng)劑，通過(guò)模擬NAADP的?理作?發(fā)揮作?。TPC2-A1-N可誘導(dǎo)TPC2顯著的Ca2+響應(yīng)(EC50=7.8μM)，這種響應(yīng)并可被?些TPC阻斷劑阻斷。TPC2-A1-N可?于檢測(cè)完整細(xì)胞中TPC2通道的不同功能。IC50&TargetEC50:10.5μM(Ca2+currentresponsefromTPC2)[1]體外研究Two-porechannels(TPC1-3)areancientmembersofthevoltage-gatedionchannelsuperfamily.TPCsareexpressedthroughouttheendo-lysosomalsystemandregulatesthetraffickingofvariouscargoes.TPC2canmediatedifferentphysiologicalandpossiblypathophysiologicaleffectsdependingonhowitisactivated.TheionselectivityofTPC2isnotfixedbutratheragonist-dependent.TPC2isauniqueexampleofanionchannelthatconductsdifferentionsinresponsetodifferentactivatingligands.TPC2-A1-N(10μM)reproduciblyevokesCa2+signals,andTPC2-A1-NresponsereachsitsplateaufasterthanTPC2-A1-P.TheEC50infullconcentration-effectrelationshipsfortheplateauresponseis7.8μMforTPC2-A1-NinacelllinestablyexpressingTPC2L11A/L12A.TPC2-A1-N(10μM)evokesCa2+influxthroughtheTPC2poreevokesCa2+signalsincellsexpressingTPC2L11A/L12AbutnotTPC2L11A/L12A/L265P.Additionally,theresponsestoTPC2-A1-NcanbeselectivelyblockedbytheidentifiedTPC2blockersTetrandrine(HY-13764,Tet),Raloxifene(HY-13738,Ral),andFluphenazine(HY-A0081,Flu)byremovalofextracellularCa2+[1].Inendo-lysosomalpatch-clampexperiments,TPC2-A1-N(30μM)elicitscurrentsusingNa+asthemajorpermeantion,invacuolin-enlargedendo-lysosomesisolatedfromisolatedfromHEK293cellstransientlyexpressinghumanTPC2(hTPC2)butnotincellsexpressingTPC1[1].Inendo-lysosomalpatch-clampexperiments,TPC2-A1-N(30μM)induceslargercurrentsinendo-lysosomesisolatedfromcellsexpressingagain-of-functionvariantofTPC2(TPC2M484L)comparedtothewild-typeisoform,andexhibitsanEC50valueof0.6μMforTPC2-A1-N[1].REFERENCES[1].SusanneGerndt,etal.Agonist-mediatedswitchingofionselectivityinTPC2differentiallypromoteslysosomalfunction.Elife[2].XuhuiJin,etal.TargetingTwo-PoreChannels:CurrentProgressandFutureChallenges.TrendsPharmacolSci.2020Aug