Staurosporine-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEStaurosporineCat.No.:HY-15141CASNo.:62996-74-1分?式:C??H??N?O?分?量:466.53作?靶點(diǎn):PKC;PKA;Apoptosis;Bacterial;Fungal;Antibiotic作?通路:Epigenetics;TGF-beta/Smad;ProteinTyrosineKinase/RTK;StemCell/Wnt;Apoptosis;Anti-infection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:62.5mg/mL(133.97mM;Needultrasonic)掃描?維碼，H2O:<0.1mg/mL(insoluble)運(yùn)?溶解?案計(jì)算器獲得適合您實(shí)驗(yàn)體系的溶解?案MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.1435mL10.7174mL21.4348mL5mM0.4287mL2.1435mL4.2870mL10mM0.2143mL1.0717mL2.1435mL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(4.46mM);Clearsolution此?案可獲得≥2.08mg/mL(4.46mM，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1/4www.MedChemEwww.MedChemE2.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(4.46mM);Suspendedsolution;Needultrasonic此?案可獲得2.08mg/mL(4.46mM)的均勻懸濁液，懸濁液可?于?服和腹腔注射。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(4.46mM);Clearsolution此?案可獲得≥2.08mg/mL(4.46mM，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Staurosporine?種有效，ATP競(jìng)爭(zhēng)性的，?選擇性蛋?激酶抑制劑，抑制PKC，PKA，c-Fgr，和Phosphorylasekinase的IC50分別為6nM，15nM，2nM，3nM。Staurosporine?個(gè)凋亡誘導(dǎo)劑。IC50&TargetPKCPKAc-FgrPhosphorylasekinase6nM(IC50)15nM(IC50)2nM(IC50)3nM(IC50)S6kinase(70kDa)v-Srccdc2TPK-IIB/Syk5nM(IC50)6nM(IC50)9nM(IC50)16nM(IC50)Ca2+/CaMPK-I1MLCKIREGF-R20nM(IC50)21nM(IC50)61nM(IC50)100nM(IC50)ERK-1CSKIGF-IRCK21500nM(IC50)2000nM(IC50)6150nM(IC50)19500nM(IC50)CK1163500nM(IC50)體外研究Staurosporine,widelyusedasaproteinkinaseC(PKC)inhibitorwithabroadspectrumofactivity,isanalkaloidisolatedfromtheculturebrothofStreptomycesstaurospores.MC3T3E-1osteoblasts,exposetoStaurosporine(100nM)for12h,releaseanamountofLDH(12.4±3.1%)thatissimilartothatreleasebythecontrolcells(10.0±2.4%),indicatingtherelativeabsenceoflyticdeath,whichoccursinnecrosis.Inaddition,treatmentwithStaurosporine(100nM)resultsinmorphologicalchanges,characteristicofapoptosis:abrightbluefluorescentcondensednucleiseenthroughafluorescencemicroscopeafterHoechst33258-staining,andareductionofcellvolume[2].體內(nèi)研究TheinhibitoryeffectofStaurosporineisstatisticallysignificantataroundWk10oftumorpromotion.Althoughstatisticallysignificantinhibitionisnotobtainedwith10ngofStaurosporineinlaterweeksoftheexperiment,adecreasingtendencyinthepercentagesoftumorbearingmiceandinaveragenumbersoftumorspermouseisapparent.Thus,StaurosporineslightlyinhibitstumorpromotionofTeleocidin,evenatthedoseatwhichStaurosporineitselfinducedtumors[3].Staurosponne(0.05and0.1mg/kgintraperitoneal)attenuates2/4www.MedChemEwww.MedChemEtheimpairedperlormanceofwatermazeandpassiveavoidancetasks,eventhoughthedrugadministrationbegan2weeksafterthelesion.Moreover,Staurosporine(0.1mg/kg)partiallyreversedthedecreaseofcholineacetyltransferaseactivityinthefronto-parietalcortexinducedbybasalforebrain-lesion.TheseresultssuggestthatStaurosporineattenuatesimpairmentoflearningthroughreversalofdamagetocholinergicneuronsinducedbybasalforebrain-lesion[4].PROTOCOLAnimalMice[3]Administration[3][4]FemaleCD-Imiceareused.VariousamountsofStaurosporinein10μLofacetoneareappliedtotheearsof8-wk-oldCD-Imice.Theextentofirritationisexpressedastheminimumdoseofthecompoundcausingirritation.InductionofHOCinMouseSkinStaurosporinein0.1mLofacetoneisappliedtotheskinofthebacksofCD-Imice,andacrudeenzymeextractisobtainedfromtheskin18hlater.HDCactivityisexpressedaspmolofCO2releasedpermgofproteinperlhofincubation.InductionofODCinMouseSkinStaurosporinein0.2mLofacetoneisappliedtotheskinofthebacksofCD-Imice.After4h,acrudeenzymeextractispreparedfromtheepidermis,anditsODCactivityismeasured.EnzymeactivityisexpressedasnmolofCO2permgofproteinper30minofincubation.Rats[4]MaleKblWistarrats(weighing270to310g)areused.InthegroupwhichisgivenStaurosporinefor2weeks,

thewatermazetaskandStaurosporineadministrationarestarted2weeksaftertheBF-lesion,andthe

passiveavoidancetaskiscarriedout4weeksaftertheBFlesion.TheratreceivedStaurosporineatdosesof0.01,0.03,0.1,and0.3mg/kg(i.p.,N=10ineachgroupfor2weeks)30mmpriortothewatermazetraining

sessionsandthepassiveavoidancetaskacquisitiontrial.InthegroupwhichisgivenStaurosporinefor4

weeks,thedrugisfirstgiven2weeksaftertheBF-lesion.Thewatermazetaskiscarriedout4weeksafter

theBF-lesion.Thepassiveavoidancetaskiscarriedout6weeksaftertheBF-lesion.Theratreceived

Staurosporineat0.05,0.1,and0.2mg/kg(i.p.,N=10ineachgroup)onceadayfor2weeksbeforetraining,

andfor2weeksafterthewatermazetrainingsessionsandthepassiveavoidancetaskacquisitiontrial.

Staurosporineissuspendedin0.3%ofsodiumcarboxymethylcellulose.Thevehicleisadministeredtothe

non-lesionedcontrolsandthelesionedcontrolsonthesamescheduleastheStaurosporine-treatedanimals.

MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶(hù)使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Nature.2021Mar;591(7850):477-481.?Cell.2018Sep6;174(6):1477-1491.e19.?CellRes.2018Dec;28(12):1171-1185.?JAmChemSoc.2018Feb7;140(5):1863-1869.?SignalTransductTargetTher.2020Oct9;5(1):235.Seemorecustomervalidationsonwww.MedChemEREFERENCES3/4www.MedChemEwww.MedChemE[1].MeggioF,etal.Differentsusceptibilityofproteinkinasestostaurosporineinhibition.KineticstudiesandmolecularbasesfortheresistanceofproteinkinaseCK2.EurJBiochem.1995Nov15;234(1):317-22.[2].ChaeHJ,etal.Molecularmechanismofstaurosporine-inducedapoptosisinosteoblasts.PharmacolRes.2000Oct;42(4):373-81.[3].YoshizawaS,