Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEsRANKL-IN-3Cat.No.:HY-151347CASNo.:2412947-15-8分?式:C??H??N?O?分?量:326.31作?靶點(diǎn):RANKL/RANK;NF-κB作?通路:NF-κB儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性sRANKL-IN-3(CompoundS3-15)?種選擇性的和具有?服活性的可溶性RANKL(sRANKL)抑制劑，其IC50為0.19μM。sRANKL-IN-3可靶向抑制可溶性RANK-RANKL相互作?。sRANKL-IN-3可?于?質(zhì)疏松癥的研究。體外研究sRANKL-IN-3(CompoundS3-15)selectivelybindssRANKL.sRANKL-IN-3hasahighbindingaffinitytosRANKL(KD=5.78?μM)andissignificantlystrongerthanbinary-RANKL(KD=124?μM)[1].sRANKL-IN-3(0.01-100μM;5d;osteoclast)inhibitsosteoclastogenesisinadose-dependentmanner[1].sRANKL-IN-3(5μM;24h;osteoclast)suppressesRANKLmediatedNF-κBandMAPKsignalingpathway[1].sRANKL-IN-3(0.003-33μM;24h;osteoclast)inducesmatureosteoclastsapoptosisandattenuatesboneresorptioninadose-dependentmanner[1].sRANKL-IN-3(0.1-10μM;14days)increasescellproliferationandmineralizationinmouseembryonicmesenchymalstemcelllineC3H10T1/2orhumanprimaryosteoblastscellswithosteogenicdifferentiationmedium[1].CellViabilityAssay[1]CellLine:OsteoclastConcentration:0.01,0.1,1,10,and100μMIncubationTime:5daysResult:InhibitedosteoclastogenesiswithanIC50valueof0.19μM.ApoptosisAnalysis[1]1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellLine:MatureosteoclastsConcentration:0.003,0.01,0.03,0.1,0.3,1,310and33μMIncubationTime:24hoursResult:SignificantlyincreasedapoptosisofmatureosteoclastswithanEC50of0.55?μM.ApoptosisAnalysis[1]CellLine:C3H10T12cellsConcentration:0.1,1and10μMIncubationTime:14daysResult:IncreasedcellproliferationandmineralizationinmouseembryonicmesenchymalstemcelllineWesternBlotAnalysis[1]CellLine:OsteoclastConcentration:5μMIncubationTime:24hoursResult:ReducedNF-κBandNFATC-luciferaseexpressionandsuppressesosteoclastmarkers(DC-stamp,Ctsk,MMP9,Tracp,Oscar,andCalcr)expression.體內(nèi)研究sRANKL-IN-3(CompoundS3-15,10mg/kg/d;i.g.;12weeks)showsanti-osteoporosisactivityinovariectomyrats[1].AnimalModel:FemaleSDovariectomy(OVX)rats[1]Dosage:10mg/kg/dAdministration:Oraladministraton,12weeksResult:Reducedboneloss,improvedtrabecularosteoporosisparameters,increasedthebonevolume/totalvolume(BV/TV).AnimalModel:28-week-oldand280?g-370?gweightmaleSD(SpragueDawley)rats[1]Dosage:10mg/kgAdministration:Oralgavage(PharmacokineticStudy)2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEResult:ThepharmacokineticparametersofsRANKL-IN-3[1]sRANKL-IN-2AUC(hr*μg/mL)113.59Cmax(μg/mL)9.52T1/2(h)15.55REFERENCES[1].HuangD,etal.IdentificationofabindingsiteonsolubleRANKLthatcanbetargetedtoinhibitsolubleRANK-RANKLinteractionsandtreatosteoporosis.NatCommun.2022Sep12;13(1):5338.McePdfHeightCaution:Producthasnotbeenfullyvalidatedfor