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| MolecularWeight: | 580.67 |
| Formula: | C31H40N4O7 |
| Purity: | ≥98% |
| CAS#: | 960374-59-8 |
| Solubility: | DMSOupto100mM |
| ChemicalName: | (S)-3-(4-methoxyphenyl)-N-((S)-1-((S)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propanamide |
| Storage: | Powder:4oC1year.DMSO:4oC3month;-20oC1year. |
BIOLOGicalActivity:
ONX-0914isanimmunoproteasomeinhibitor.Itselectivelyinhibitslow–molecularmasspolypeptide-7(LMP7,encodedbyPsmb8),thechymotrypsin-likesubunitoftheimmunoproteasome,withanIC50<100nM.ItblockedpresentationofLMP7-specific,MHC-I–restrictedantigensinvitroandinvivowithminimalcross-reactivityfortheconstitutiveproteasome.SelectiveinhibitionofLMP7byONX-0914blockedproductionofinterleukin-23(IL-23)byactivatedmonocytesandinterferon-gammaandIL-2byTcells.Inmousemodelsofrheumatoidarthritisandlupus,ONX-0914treatmentreversedsignsofdiseaseandresultedinreductionsincellularinfiltration,cytokineproductionandautoantibodylevelsatwell-tolerateddoses.ONX0914isagoodchemicalprobetorevealauniqueroleforLMP7incontrollingpathogenicimmuneresponsesandprovideatherapeuticrationaleforautoimmunedisorders,suchasrheumatoidarthritis,inflammatoryboweldiseaseandlupus.
HowtoUse:
- Invitro:ONX-0914wasusedat0.1-0.3µMinvitroandincellularassays.
- Invivo:ONX-0914wasdosedtomicebyeitherintravenousorsubcutaneousadmiNISTrationat2-10mg/kgonceadayfor5days.
Reference:
- 1.MuchamuelT,etal.AselectiveinhibitoroftheimmunoproteasomesubunitLMP7blockscytokineproductionandattenuatesprogressionofexperimentalarthritis.(2009)NatMed.15(7):781-7.
- 2.BaslerM,etal.Preventionofexperimentalcolitisbyaselectiveinhibitoroftheimmunoproteasome.(2010)JImmunol.185(1):634-41.
- 3.HuberEM,etal.Immuno-andconstitutiveproteasomecrystalstructuresrevealdifferencesinsubstrateandinhibitorspecificity.(2012)Cell.148(4):727-38.
- 4.KalimKW,etal.ImmunoproteasomesubunitLMP7deficiencyandinhibitionsuppressesTh1andTh17butenhancesregulatoryTcelldifferentiation.(2012)JImmunol.189(8):4182-93.
ONX-0914_spec.pdf- ONX-0914_MSDS.pdf
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