TPC2-A1-N-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrariesTPC2-A1-NCat.No.:HY-131614CASNo.:136186-07-7分⼦式:C₁₇H₉Cl₂F₃N₂O₂分⼦量:401.17作⽤靶点:CalciumChannel作⽤通路:MembraneTransporter/IonChannel;NeuronalSignaling储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:250mg/mL(623.18mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.4927mL12.4635mL24.9271mL5mM0.4985mL2.4927mL4.9854mL10mM0.2493mL1.2464mL2.4927mL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，并请注意储备液的保存⽅式和期限。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%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.08mg/mL(5.18mM);Clearsolution此⽅案可获得≥2.08mg/mL(5.18mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL20.8mg/mL的澄DMSO储备液加到400μLPEG300中，混合均匀；向上述2.体系中加⼊50μLTween-80，混合均匀；然后继续加⼊450μL⽣理盐⽔定容⾄1mL。请依序添加每种溶剂：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(5.18mM);Clearsolution1/3此⽅案可获得≥2.08mg/mL(5.18mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL20.8mg/mL的澄DMSO储备液加到900μL20%的SBE-β-CD⽣理盐⽔⽔溶3.液中，混合均匀。请依序添加每种溶剂：10%DMSO90%cornoilSolubility:≥2.08mg/mL(5.18mM);Clearsolution此⽅案可获得≥2.08mg/mL(5.18mM，饱和度未知)的澄溶液，此⽅案不适⽤于实验周期在半个⽉以上的实验。以1mL⼯作液为例，取100μL20.8mg/mL的澄DMSO储备液加到900μL⽟⽶油中，混合均匀。BIOLOGICALACTIVITY⽣物活性TPC2-A1-N⼀种强⼤的Ca2+-可渗透双孔通道2(TPC2)的激动剂，通过模拟NAADP的⽣理作⽤发挥作⽤。TPC2-A1-N可诱导TPC2显著的Ca2+响应(EC50=7.8μM)，这种响应并可被⼀些TPC阻断剂阻断。TPC2-A1-N可⽤于检测完整细胞中TPC2通道的不同功能。IC50&TargetEC50:10.5μM(Ca2+currentresponsefromTPC2)[1]体外研究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