RO8323
RO8323 is an orally active, selective CDK8/CDK19 inhibitor, with an IC50 of 2 nM against CDK8 and 3 nM against CDK19. RO8323 promotes regulatory T cell differentiation, inhibits effector T cell generation, reverses the Teff/Treg ratio, upregulates IL-10 production in myeloid cells, and suppresses the production of TNF-α, IL-6 and IL-12. RO8323 enhances immune reconstitution and prolongs cardiac allograft survival in a dose-dependent manner. RO8323 can be used in the research of chronic graft-versus-host disease, cardiac allograft rejection, acute graft-versus-host disease and experimental autoimmune encephalomyelitis.
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- Formule: C19H17N5
- Masse moléculaire:315.37
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
- Pureté et documentation
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Activité biologique
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CDK8 2 nM (IC50) |
CDK19 3 nM (IC50) |
IL-10 |
IL-6 |
IL-12 |
RO8323 potently and selectively inhibits purified CDK8 (IC50 = 2 nM) and CDK19 (IC50 = 3 nM) enzymes, with over 100-fold selectivity against the kinome[1].
RO8323 (0.01-1 μM; 4 days) dose-dependently enhances the differentiation of CD25+Foxp3+ regulatory T cells (Treg) from naive mouse CD4+T cells. After treatment with 1 μM RO8323 for 4 days, the differentiation level increases by 1.3-fold compared with that of the control, and the functional markers of Treg are simultaneously upregulated[1].
RO8323 (0.01-1 μM; 6 days) dose-dependently promotes the differentiation of CD25+Foxp3+ regulatory T cells (Treg) in hCD4+ T cells. After treatment with 1 μM RO8323 for 6 days, the differentiation level increases by 1.6-fold compared with that of the control, while the functional markers of Treg are upregulated[1].
RO8323 (0.01-1 μM; 18 h) dose-dependently enhances IL-10 production and suppresses the expression of proinflammatory cytokines (TNF-α, IL-6, IL-12) in R848-stimulated monocyte-derived dendritic cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
RO8323 (3-10 mg·kg-1·d-1; oral gavage; daily; from day 0 to day 20 post-transplantation) dose-dependently prolongs cardiac allograft survival in mouse models, with a survival rate of 90% observed in the 10 mg·kg-1·d-1 group, accompanied by persistent expansion of regulatory T cells (Treg)[1].
RO8323 (10 mg·kg-1·d-1; oral gavage; daily; day 0 post-induction) completely prevents disease onset in mouse MOG-induced EAE models, increases the frequency of peripheral Tregs by 1.7-fold, and suppresses pathogenic Th1 and Th17 cell populations[1].
RO8323 (1-30 mg·kg-1; oral gavage; single administration; 30 minutes prior to LPS challenge) dose-dependently increases the serum IL-10 levels in LPS-challenged mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c (male, 7-9 weeks old, cGVHD model via sublethal 6.5 Gy irradiation + intravenous transfer of 5×106 T cell-depleted bone marrow cells plus 40×106 CD25-depleted splenocytes from allogeneic DBA/2 donors)[1]
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Dosage:3 mg·kg-1·d-1
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Administration:i.g.; daily; day 7 to day 49 post-transplantation
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Result:Achieved 100% survival (vs. 36% in allogeneic vehicle controls).
Reduced proteinuria, as shown by lower area under the curve values and reduced peak proteinuria levels.
Reversed glomerulosclerosis and mesangial matrix lesions, resulting in significantly lower renal histopathology scores.
Suppressed renal inflammatory mediators BAFF, MCP-1, and CXCL10 by 68%, 69%, and 75% respectively.
Showed a non-significant increasing trend in peripheral CD25+Foxp3+ Treg frequencies.
Uniquely restored multi-lineage immune reconstitution (CD45+ leukocytes, CD4+ T cells, CD8+ T cells, B cells, monocytes, NK cells) compared to allogeneic vehicle controls.
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Animal Model:C3H/HeN (male, 6-8 weeks old, cardiac allograft rejection model via neonatal BALB/c mouse hearts implanted into ear pinnas)[1]
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Dosage:3 mg·kg-1·d-1; 10 mg·kg-1·d-1
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Administration:i.g.; daily; day 0 to day 20 post-transplantation
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Result:Dose-dependently prolonged cardiac allograft survival, with 50% graft survival at the 3 mg·kg-1·d-1 dose and 90% graft survival at the 10 mg·kg-1·d-1 dose at day 20 post-transplantation (vs. 20% in untreated allograft controls).
Increased peripheral CD25+Foxp3+ Treg frequencies to 2-fold at the 10 mg·kg-1·d-1 dose by day 10 post-transplantation, with effects persisting to day 20 (3-fold increase).
Chemical Information
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Masse moléculaire 315.37
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Formule C19H17N5
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SMILES
N12C=CC(C3=NN=CN3CCCC4=CC5=CC=C4)=CC1=C(C5)N=C2
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
RO8323 Related Classifications
HY-183074 Related Classifications
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