In vitro activity: Mizoribine (1-50 mg/mL) is able to inhibit T cell proliferation by 10-100% in a dose-dependent fashion to all stimuli tested. Mizoribine leads to a decrease in intracellular GTP levels, and that repletion of GTP reversed its antiproliferative effects Mizoribine causes a dose-dependent inhibition of T cell proliferation, which is reversible with the addition of 50 mM guanosine to replete guanine ribonucleotide pools. Mizoribine selectively inhibits guanine ribonucleotide formation in purified T cells, whereas the effect of 6-mercaptopurine (6MP) appears to be more dependent on adenine ribonucleotide depletion. Mizoribine inhibits HCV RNA replication with IC50 of 100 μM.

Cell Assay: Unlike azathioprine, Mizoribine is not taken up by nucleic acids in the cell. Instead, after phosphorylation MZR-5 -monophosphate inhibits GMP synthesis by the antagonistic blocking of IMPDH (Ki = 10(-8)M) and GMP- synthetase (Ki =10(-5) M). Pretreatment of cells with MZR partially, but significantly, attenuates the expression of monocyte chemoattractant protein (MCP)-1 mRNA and protein, whereas the poly IC-induced expressions for the other functional molecules, such as CCL5, fractalkine and IL-8 were not influenced by MZR treatment.

Mol Pharmacol. 1992 Apr;41(4):671-6; Nephrol Dial Transplant. 2005 Aug;20(8):1573-81.