Cat. No.: HY-114438

PR-825

PR-825 is a selective constitutive proteasome β5 chymotrypsin-like active site inhibitor with an IC₅₀ value of 17 nM for X/β5. PR-825 reduces MHC-I expression. PR-825 has no effect on collagen antibody-induced arthritis. PR-825 delays the onset and reduces the severity of experimental autoimmune encephalomyelitis in LMP7-deficient mice while inhibiting IFN-γ/IL-17 production, but has no such effect in wild-type mice.

For research use only. We do not sell to patients.

CAS No.: 935888-08-7
Formula: C₂₂H₃₄N₄O₈
Molecular Weight:482.53

Storage:

Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (289 KB)

PR-825 Chemical Structure

CAS No.: 935888-08-7

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Purity & Documentation
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

Description

IC₅₀ & Target

^[8]^[1]

IL-17

MHC I

All MHC Isoforms :

MHC I
MHC II

All Interleukin Related Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
MES-SA	IC₅₀	145 nM Compound: 49	Cytotoxicity against multidrug resistance transporter expressing doxorubicin resistant human MESSA cells assessed as cell viability after 72 hrs by CellTiter-Glo luminescent assay Cytotoxicity against multidrug resistance transporter expressing doxorubicin resistant human MESSA cells assessed as cell viability after 72 hrs by CellTiter-Glo luminescent assay	[PMID: 19348473]
MES-SA	IC₅₀	22 nM Compound: 49	Cytotoxicity against human MESSA cells assessed as cell viability after 72 hrs by CellTiter-Glo luminescent assay Cytotoxicity against human MESSA cells assessed as cell viability after 72 hrs by CellTiter-Glo luminescent assay	[PMID: 19348473]
MOLT-4	IC₅₀	48 nM Compound: 49	Inhibition of chymotrypsin-like activity of 20S proteasome in human MOLT4 cells after 1 hr by CellTiter-Glo luminescent assay Inhibition of chymotrypsin-like activity of 20S proteasome in human MOLT4 cells after 1 hr by CellTiter-Glo luminescent assay	[PMID: 19348473]

In Vitro

Adaptive ImmunityCytokines & ChemokinesCytokines and ChemokinesInnate ImmunityViral InfectionProtein/Amino Acid Metabolism

Adaptive Immunity

PR-825 reduces MHC-I expression on splenocytes from Psmb8^−/− mice^[1].

Adaptive Immunity

Cytokines & Chemokines

PR-825 (125 nM; 1 h) inhibits anti-CD3-induced IL-17 and IFN-γ secretion in splenic CD4⁺ T cells from LMP7-deficient mice, but has no such effect in WT C57BL/6 CD4⁺ T cells^[4].

Adaptive Immunity

Cytokines and Chemokines

PR-825 does not affect the production of IFN-γ or IL-2 by CD3/CD28-stimulated PBMCs^[1].

Innate Immunity

Adaptive Immunity

Cytokines & Chemokines

Viral Infection

PR-825 (125 nM) does not reduce the presentation of GP118-125 by LCMV-infected LMP7^-/- thioglycolate-induced macrophages^[5].

Innate Immunity

Adaptive Immunity

Viral Infection

PR-825 (125 nM) does not reduce the presentation of GP118-125 by LCMV-infected C57BL/6 Thioglycolate (HY-W115724)-induced macrophages^[5].

Innate Immunity

Cytokines & Chemokines

PR-825 (125 nM; 1 h) only slightly reduces LPS-induced Cd14, Tlr2, and Tnf expression in ex vivo CD11b⁺ microglia from 15-month-old APPswePS1dE9 and wild-type mice^[7].

Innate Immunity

Cytokines and Chemokines

PR-825 does not significantly alter LPS-induced IL-23, TNF-α, or IL-6 production in PBMCs^[1].

Innate Immunity

Protein/Amino Acid Metabolism

PR-825 inhibits chymotrypsin-like proteasome activity in Thioglycolate-induced macrophages^[5].

Protein/Amino Acid Metabolism

PR-825 selectively inhibits β5 in PBMCs, while showing weaker inhibition of LMP7, LMP2, MECL-1, β1, and β2^[1].
PR-825 is a potent X/β5 inhibitor with an IC₅₀ of 17 nM in purified 20S proteasome and shows weaker inhibitory activity against LMP7/β5i, LMP2/β1i, and Y/β1^[9].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Adaptive ImmunityImmune Tolerance & ImmunosuppressionInnate ImmunityViral InfectionCytokines & ChemokinesOthers

Adaptive Immunity

PR-825 suppresses EAE in β5i^−/− mice, indicating that blocking chymotrypsin-like activity when β5 occupies the β5/β5i position can prevent disease^[3].

Adaptive Immunity

Immune Tolerance & Immunosuppression

PR-825 (2 mg/kg; s.c.; three times per week; beginning on the day of immunization) does not alter MOG_35-55-induced EAE onset or severity in wild-type C57BL/6 mice^[2].
PR-825 (1 mg/kg; s.c.; three times per week; beginning on the day of immunization) delays EAE onset and reduces disease severity in LMP7^−/− mice^[2].
PR-825 does not prevent MOG_35-55-induced EAE in wild-type mice but almost completely protects LMP7-deficient mice from disease^[8].

Innate Immunity

PR-825 (twice weekly; 3 weeks) produces only mild improvement in Morris water maze performance in LPS-treated ICR mice^[9].

Viral Infection

Adaptive Immunity

Cytokines & Chemokines

PR-825 (2 mg/kg; s.c. bolus) does not impair the GP_118-125-specific CTL response but reduces the GP_33-41- and NP_396-404-specific responses in LCMV-infected C57BL/6 mice^[5].

Others

PR-825 (2 mg/kg; s.c.; once daily; 21 d) does not attenuate DSS-induced body weight loss in C57BL/6 mice^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

C57BL/6 (female, 6-10 weeks)^[2]
Dosage:

2 mg/kg
Administration:

s.c.; three times per week; beginning on the day of immunization
Result:

No change in disease onset or severity was noted in wild-type C57BL/6 mice compared with vehicle-treated mice.

Animal Model:

LMP7−/− (6-10 weeks)^[2]
Dosage:

1 mg/kg
Administration:

s.c.; three times per week; beginning on the day of immunization
Result:

LMP7−/− mice showed later disease onset and lower disease severity than vehicle-treated LMP7−/− mice.

Animal Model:

C57BL/6 (female; 8-10 wk at colitis induction)^[4]
Dosage:

2 mg/kg
Administration:

s.c.; once daily; 21 d
Result:

Body weight loss was similar to that of vehicle-treated mice over the 21-day DSS colitis experiment.

Animal Model:

C57BL/6 (H-2b, 6-10 weeks of age)^[5]
Dosage:

2 mg/kg
Administration:

s.c. bolus
Result:

Did not affect the GP118-125-specific CTL response on day 8 after LCMV-WE infection.
Reduced the GP33-41-specific CTL response and also reduced the NP396-404-specific CTL response.

Related Protocols :

Chemical Information

CAS No. 935888-08-7
Molecular Weight 482.53
Formula C₂₂H₃₄N₄O₈
SMILES

O=C(C1=NOC(C)=C1)N[C@@H](COC)C(N[C@@H](COC)C(N[C@@H](CC(C)C)C([C@]2(CO2)C)=O)=O)=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (289 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Muchamuel T, et al. A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nature medicine. 2009 Jul;15(7):781-7. [Content Brief]

[2]. Basler M, et al. Inhibition of the immunoproteasome ameliorates experimental autoimmune encephalomyelitis. EMBO molecular medicine. 2014 Feb;6(2):226-38.

[3]. Kisselev AF, et al. Subunit specific inhibitors of proteasomes and their potential for immunomodulation. Current opinion in chemical biology. 2014 Dec 1;23:16-22.

[4]. Basler M, et al. Prevention of experimental colitis by a selective inhibitor of the immunoproteasome. Journal of immunology (Baltimore, Md. : 1950). 2010 Jul 01;185(1):634-41.

[5]. Basler M, et al. The immunoproteasome subunit LMP7 is required in the murine thymus for filling up a hole in the T cell repertoire. European journal of immunology. 2018 Mar;48(3):419-29.

[6]. Schmidt C, et al. Immunoproteasome inhibition impairs T and B cell activation by restraining ERK signaling and proteostasis. Frontiers in immunology. 2018 Oct 26;9:2386.

[7]. Orre M, et al. Reactive glia show increased immunoproteasome activity in Alzheimer's disease. Brain : a journal of neurology. 2013 May;136(Pt 5):1415-31.

[8]. Basler M, et al. The immunoproteasome: a novel drug target for autoimmune diseases. Clinical and experimental rheumatology. 2015;33(4 Suppl 92):S74-9.

[9]. Yeo IJ, et al. A dual inhibitor of the proteasome catalytic subunits LMP2 and Y attenuates disease progression in mouse models of Alzheimer's disease. Scientific reports. 2019 Dec 05;9(1):18393.

Calculators

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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PR-825

All MHC Isoforms

All Interleukin Related Isoforms