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.
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 分子式: C19H17N5
- 分子量:315.37
-
保管条件:
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]
-
生物活性
-
化学情報
- プロトコル
- 純度とドキュメンテーション
- 参考文献
-
Help & FAQs
生物活性
製品説明
IC50 & Target
[1]|
CDK8 2 nM (IC50) |
CDK19 3 nM (IC50) |
IL-10 |
IL-6 |
IL-12 |
体外実験
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. Further protocols information, click here.
体内実験
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.
-
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]
-
Dosage:3 mg·kg-1·d-1
-
Administration:i.g.; daily; day 7 to day 49 post-transplantation
-
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.
-
Animal Model:C3H/HeN (male, 6-8 weeks old, cardiac allograft rejection model via neonatal BALB/c mouse hearts implanted into ear pinnas)[1]
-
Dosage:3 mg·kg-1·d-1; 10 mg·kg-1·d-1
-
Administration:i.g.; daily; day 0 to day 20 post-transplantation
-
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).
化学情報
-
分子量 315.37
-
分子式 C19H17N5
-
SMILES
N12C=CC(C3=NN=CN3CCCC4=CC5=CC=C4)=CC1=C(C5)N=C2
-
輸送条件
Room temperature in continental US; may vary elsewhere.
-
保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
プロトコル
-
Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
-
Naïve CD4+ T-cell subset differentiation/polarization
Naïve CD4+ T-cell subset differentiation/polarization is an in vitro assay in which purified naïve CD4+ T cells are activated through TCR and CD28 costimulation and cultured with defined cytokines and neutralizing antibodies to generate Th0, Th1, Th2, Th17, or induced Treg-like populations. Differentiation is detected by subset-associated cytokines and transcription factors: IFN-γ/T-bet for Th1, IL-4/GATA3 for Th2, IL-17A/RORγt for Th17, and Foxp3 for induced Treg cells. The assay readout is usually generated by intracellular cytokine staining after restimulation, transcription-factor staining by flow cytometry, ELISA of secreted cytokines, or gene-expression analysis. The result reflects cytokine-directed lineage commitment or polarization rather than antigen-specific immune protection by itself.
-
iPSC cell differentiation
Induced pluripotent stem cells (iPSCs) are a type of cell that has similar properties to embryonic stem cells through somatic cell reprogramming.
-
Research Protocol for Cancer Immunology
Cancer immunology studies how the immune system recognizes, suppresses, edits, or fails to eliminate malignant cells through tumor antigen release, antigen presentation, T-cell priming, immune trafficking, tumor-cell killing, and feedback inhibition in the tumor microenvironment. The cancer-immunity cycle links tumor antigenicity, dendritic-cell priming, CD8+ T-cell infiltration, cytotoxic function, and immune-checkpoint regulation to tumor rejection or immune escape. Immune-checkpoint pathways such as PD-1/PD-L1 and CTLA-4 suppress antitumor T-cell activity and can be therapeutically blocked, but many tumors remain resistant because of poor antigen presentation, weak T-cell infiltration, suppressive myeloid cells, regulatory T cells, and tumor-intrinsic immune-exclusion programs. Unresolved questions include which immune-cell states predict response, how tumor-intrinsic pathways exclude immune cells, how myeloid suppression limits checkpoint blockade, and which combination strategies
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
RO8323 関連分類
HY-183074 関連分類
Powered by Bioz