L-006235-L-235-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEL-006235Cat.No.:HY-103352CASNo.:294623-49-7Synonyms:L-235分?式:C??H??N?O?S分?量:466.6作?靶點(diǎn):Cathepsin作?通路:MetabolicEnzyme/Protease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:31.25mg/mL(66.97mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.1432mL10.7158mL21.4316mL5mM0.4286mL2.1432mL4.2863mL10mM0.2143mL1.0716mL2.1432mL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；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。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?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(4.46mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.46mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.46mM);ClearsolutionBIOLOGICALACTIVITY?物活性L-006235(L-235)?種有效，選擇性，可逆和具有?服活性的cathepsinK抑制劑，在?吸收試驗(yàn)中的IC50值為5nM。L-006235顯?出cathepsinK(Ki=0.2nM)相對(duì)于cathepsinB，cathepsinL和cathepsinS的選擇性(Ki=1,6,47μM)。L-006235可減少膠原蛋?降解并防??質(zhì)流失。IC50&TargetIC50:5nM(cathepsinK)[1]體外研究L-006235inhibitsboneresorptionintherabbitboneresorptionassay,withanIC50of5nM[1].L-006235(10μM;1h)showapunctatefluorescencethroughoutthecytoplasminHepG2cells[2].體內(nèi)研究L-006235(0.6-15mg/kg;p.o.qdfor8-11d)reducesN-telopeptides(NTx)andcreatinine(Cre)byupto76%dose-dependentlyinrhesusmonkey[1].L-006235(20mg/kg;p.o.)exhibitshighoralbioavailability(68%),longterminalhalf-life(204min)andCmax(1.4μM)inrats[1].AnimalModel:Rhesusmonkey(15years)receivingoophorectomy(OVX)[1]Dosage:0.6,3,15mg/kgAdministration:P.ooncedailyfor8-11daysResult:DecreaseduNTx/Crebyanaverageof76%,68%,and31%atthedoseof15,3,and0.6mg/kg,respectively.REFERENCES[1].PalmerJT,et,al.Designandsynthesisoftri-ringP3benzamide-containingaminonitrilesaspotent,selective,orallyeffectiveinhibitorsofcathepsinK.JMedChem.2005Dec1;48(24):7520-34.[2].FalgueyretJP,et,al.LysosomotropismofbasiccathepsinKinhibitorscontributestoincreasedcellularpotenciesagainstoff-targetcathepsinsandreducedfunctionalselectivity.JMedChem.2005Dec1;48(24):7535-43.[3].PennypackerBL,et,al.CathepsinKinhibitorspreventbonelossinestrogen-deficientrabbits.JBoneMinerRes.2011Feb;26(2):252-62.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalap