NFAT Transcription Factor Regulator 是一种 IL-2 合成抑制剂，IC50 为 182 nM。
NFAT Transcription Factor Regulator is an IL-2 synthesis inhibitor with an IC50 of 182 nM.
NFAT Transcription Factor Regulator is compound example 19. NFAT Transcription Factor Regulator inhibits IL-2 synthesis with an IC50 of 182 nM. It inhibits human and rat PBMC proliferation with IC50s of 82 and 146 nM, respectively. It is able to inhibit IL-4 and IL-5 production in human T-cell lines with similar potency to its effects on IL-2 release[1].
NFAT Transcription Factor Regulator is found to have an inhibitory potency approximately 10-fold better than that of cyclosporine. Comparable inhibitory effects on T-cell IL-2 production are obtained with NFAT Transcription Factor Regulator and cyclosporine at doses of 3.0 and 30 mg/kg, po, respectively. The efficacies achieved in monkeys in vivo for blocking T-cell cytokine production suggest that NFAT Transcription Factor Regulator has potential similar to that of cyclosporine for use in transplantation[1].
[1]. Djuric SW, et al. 3,5-Bis(trifluoromethyl)pyrazoles: a novel class of NFAT transcription factor regulator. J Med Chem. 2000 Aug 10;43(16):2975-81.
Animal experiment: | Monkey[1]Cynomolgus monkeys are bled to obtain heparinized baseline samples for measuring predrug cytokine production and then briefly intubated for intragastric dosing. Cyclosporine is administered in the Neoral formulation. Compound 19 is given. Postdrug blood samples are similarly obtained 2 h later. The samples are stimulated by spiking undiluted blood with PMA (50 ng/mL) and ionomycin (1μg/mL) and incubating for 24 h. Plasma samples are collected by centrifugation, and IL-2 concentrations are determined by ELISA using recombinant human IL-2 as standard[1]. |
参考文献: [1]. Djuric SW, et al. 3,5-Bis(trifluoromethyl)pyrazoles: a novel class of NFAT transcription factor regulator. J Med Chem. 2000 Aug 10;43(16):2975-81. | |
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