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^[1].

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 mg·kg^-1·d^-1; oral gavage; daily; from day 7 to day 49 post-transplantation) achieves 100% survival rate in a mouse model of chronic graft-versus-host disease (cGVHD), alleviates renal pathological damage, inhibits inflammatory mediators, and restores multi-lineage immune reconstitution^[1].
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.

315.37

C₁₉H₁₇N₅

N12C=CC(C3=NN=CN3CCCC4=CC5=CC=C4)=CC1=C(C5)N=C2

Room temperature in continental US; may vary elsewhere.

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

• [1]. Shen F, et al. A novel CDK8/19 inhibitor RO8323 mitigates allograft rejection through dual mechanisms of action to modulate regulatory T cell and myeloid cell. Acta Pharmacol Sin. Published online March 31, 2026.