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当前位置： 首页 > 产品中心 > Small_molecule > Medchemexpress/NPS-2143(Synonyms: SB 262470A)/HY-10007/100mg
商品详细Medchemexpress/NPS-2143(Synonyms: SB 262470A)/HY-10007/100mg
Medchemexpress/NPS-2143(Synonyms: SB 262470A)/HY-10007/100mg
Medchemexpress/NPS-2143(Synonyms: SB 262470A)/HY-10007/100mg
商品编号： HY-10007-10mM*1mLinDMSO
品牌： MedChemExp
市场价： ¥2120.00
美元价： 1272.00
产地： 美国(厂家直采)
公司：
产品分类： 小分子
公司分类： Small_molecule
联系Q Q： 3392242852
电话号码： 4000-520-616
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商品介绍
NPS-2143isanovelpotentandselectiveantagoNISTof Ca2+receptor with IC50 of43nM.

CustomerValidation

  • •AmJPhysiolHeartCircPhysiol.2010Nov;299(5):H1309-17.
Description

NPS-2143isanovelpotentandselectiveantagonistof Ca2+receptor with IC50 of43nM.

IC50&Target

IC50:43nM(Ca2+receptor)

InVitro

NPS-2143blocksincreasesincytoplasmicCa2+ concentrationswithIC50of43nMelicitedbyactivatingtheCa2+receptorinHEK293cellsexpressingthehumanCa2+ receptor. NPS-2143stimulatesparathyroidhormone(PTH)secretionfrombovineparathyroidcellswithEC50of41nM.Moreover,NPS214alsoblockstheinhibitoryeffectsofcalcimimeticNPSR-467onPTHsecretionfrombovineparathyroidcellsandtheinhibitoryeffectsofextracellularCa2+onisoproterenol-stimulatedincreasesincyclicAMPformation[1]. InHEK-293cellstransientlyexpressinghCaSRs,NPS-2143significantlysuppressesthekokumitastebyeffectivelyinhibitingtheactivityofbothGSHandγ-Glu-Val-Gly[3]. ArecentstudyshowsthatNPS-2143treatmentsuppresseslowmolecularweightfractionsofazukihydrolysate-inducedcholecystokinin(CCK)secretioninCaSR-transfectedHEK293cells[4].

InVivo

NPS-2143resultsinarapid4-to5-foldincreaseinplasmaPTHlevelsandalsoatransientincreaseinplasmaCa2+ levels[1]inrats. Innormotensiverats,NPS-2143administration(1mg/kg,i.v.)markedlyincreasesmeanarterialbloodpressure(MAP)inthepresenceofparathyroidglands[2].

References

  • [1].NemethEF,etal.Calcilyticcompounds:potentandselectiveCa2+receptorantagoniststhatstimulatesecretionofparathyroidhormone.JPharmacolExpTher.2001Oct;299(1):323-31.

    [2].RybczynskaA,etal.HypertensiveeffectofcalcilyticNPS2143administrationinrats.JEndocrinol.2006Oct;191(1):189-95.

    [3].OhsuT,etal.Involvementofthecalcium-sensingreceptorinhumantasteperception.JBiolChem.2010Jan8;285(2):1016-22.

    [4].NakajimaS,etal.Calcium-sensingreceptormediatesdietarypeptide-inducedCCKsecretioninenteroendocrineSTC-1cells.MolNutrFoodRes.2012May;56(5):753-60.

    [5].SunJ,etal.Calcium-sensingreceptor:asensorandmediatorofischemicpreconditioningintheheart.AmJPhysiolHeartCircPhysiol.2010Nov;299(5):H1309-17.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM2.4455mL12.2273mL24.4547mL
5mM0.4891mL2.4455mL4.8909mL
10mM0.2445mL1.2227mL2.4455mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
KinaseAssay
[1]

Thisclonalcellline,referredtoasHEK2934.0-7cells,areusedinahigh-throughputscreeningformattodetectagonistsandallostericactivatorsoftheCa2+ receptor.Changesintheconcentrationofcytoplasmic[Ca2+]iprovideaquantitativeandfunctionalassessmentofCa2+receptoractivityinthesecellsandtheresultsusingthisassayparallelthoseobtainedusingahomologousexpressionsystemofbovineparathyroidcells.On-linecontinuousmeasurementsoffluorescenceinfluo-3-orfura-2-loadedHEK2934.0-7cellsareobtainedusingacustom-builtspectrofluorimeterorafluorescenceimagingplatereaderinstrument.NPS-2143isincubatedwithcellsfor1minutebeforeincreasingtheconcentrationofextracellularCa2+ from1.0mMto1.75mM.NPS-2143istestedindividuallyataconcentrationof100μg/mL(20μM-80μM)andthosecausingmorethana40%inhibitionofthecontrolresponseareconsideredtobeBIOLOGicallyactive.Todeterminethepotencies(IC50)ofNPS-2143withbiologicalactivity,concentration-responsecurvesareobtainedandthen,asaninitialassessmentofselectivity,theeffectsofNPS-2143on[Ca2+]ievokedbyotherGprotein-coupledreceptorsareexaminedataconcentrationseveraltimestheirIC50.Wild-typeHEK293cells(andHEK2934.0-7cells)expressreceptorsforthrombin,bradykinin,andATP,whichcoupletothemobilizationofintracellularCa2+.TheseresponsescanbestudiedtoquicklyassessanynonselectiveactionofcompoundsonGprotein-coupledreceptors.AdditionalassaysforselectivityincludeHEK293cellsengineeredtoexpressreceptorsmosthomologousinsequenceandtopologytotheCa2+receptor.Theseincludenativeorchimericreceptorsforvariousmetabotropicglutamateandγ-aminobutyricacidtypeBreceptors(GABABRs).ChimericreceptorsarecreatedusingpartialsequencesofmetabotropicglutamatereceptorsandCa2+ receptors,engineeredtocoupletoactivationofphospholipaseCandreleaseofintracellularCa2+ inHEK293cells.NPS-2143lackingpan-activityarethensubjectedtostructuralmodificationsandtheirpotenciesandselectivitiesmonitoredusingtheseHEK2934.0-7cellassaysinaniterativeprocess.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdministration
[1]

NPS-2143isformulatedin20%aqueoussolutionof2-hydroxypropyl-β-cyclodextrin.

Onthedayofstudy,theratsareinfusedintravenously(0.1mL/kg·min)for120minwithNPS-2143(0.1μmol/kg·min)orvehicle,a20%aqueoussolutionof2-hydroxypropyl-β-cyclodextrin.Bloodsamples(0.5mL)arecollectedbeforeandatvarioustimesafterthestartoftheinfusionformeasurementsofplasmalevelsofPTHandCa2+.Topreventexcessivebloodvolumelossduringthecourseoftheexperiment,foreachbloodsampletheerythrocytepelletisresUSPendedinanequalvolumeofnormalratplasmaandreinjected.PlasmalevelsofCa2+ aremeasuredimmediatelyaftercollectionusingamodel634ionizedcalciumanalyzer.PTHlevelsaremeasuredusingtheImmutopicsratPTH(1-34)immunorADIometricassaykit.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References

  • [1].NemethEF,etal.Calcilyticcompounds:potentandselectiveCa2+receptorantagoniststhatstimulatesecretionofparathyroidhormone.JPharmacolExpTher.2001Oct;299(1):323-31.

    [2].RybczynskaA,etal.HypertensiveeffectofcalcilyticNPS2143administrationinrats.JEndocrinol.2006Oct;191(1):189-95.

    [3].OhsuT,etal.Involvementofthecalcium-sensingreceptorinhumantasteperception.JBiolChem.2010Jan8;285(2):1016-22.

    [4].NakajimaS,etal.Calcium-sensingreceptormediatesdietarypeptide-inducedCCKsecretioninenteroendocrineSTC-1cells.MolNutrFoodRes.2012May;56(5):753-60.

    [5].SunJ,etal.Calcium-sensingreceptor:asensorandmediatorofischemicpreconditioningintheheart.AmJPhysiolHeartCircPhysiol.2010Nov;299(5):H1309-17.

MolecularWeight

408.92

Formula

C₂₄H₂₅ClN₂O₂

CASNo.

284035-33-2

Storage
Powder-20°C3years
 4°C2years
Insolvent-80°C6months
 -20°C1month
Shipping

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

10mMinDMSO

NPS-2143isdissolvedintoDMSOas10mMofstocksolution,andaliquotsaredilutedinto100mLperfusionbufferjustbeforeuse[5].

*"<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">

References

  • [1].NemethEF,etal.Calcilyticcompounds:potentandselectiveCa2+receptorantagoniststhatstimulatesecretionofparathyroidhormone.JPharmacolExpTher.2001Oct;299(1):323-31.

    [2].RybczynskaA,etal.HypertensiveeffectofcalcilyticNPS2143administrationinrats.JEndocrinol.2006Oct;191(1):189-95.

    [3].OhsuT,etal.Involvementofthecalcium-sensingreceptorinhumantasteperception.JBiolChem.2010Jan8;285(2):1016-22.

    [4].NakajimaS,etal.Calcium-sensingreceptormediatesdietarypeptide-inducedCCKsecretioninenteroendocrineSTC-1cells.MolNutrFoodRes.2012May;56(5):753-60.

    [5].SunJ,etal.Calcium-sensingreceptor:asensorandmediatorofischemicpreconditioningintheheart.AmJPhysiolHeartCircPhysiol.2010Nov;299(5):H1309-17.

Purity:99.42%