MLT-943 is a potent, selective, and orally active inhibitor of MALT1 protease. It inhibits stimulated IL-2 secretion in PBMC or whole blood with a consistent IC50 across species (0.07-0.09 μM in PBMC, 0.6-0.8 μM in whole blood). MLT-943 possesses anti-inflammatory properties and is suitable for research on FcγR-mediated inflammation[1].
体内研究
MLT-943 prophylactic treatment (oral gavage; 10 mg/kg; QD) suppresses anti-collagen antibody production, completely prevents paw swelling, and restores joint histology scores to normal levels in the rat collagen-induced arthritis model[1].
MLT-943 (oral gavage; 5 mg/kg; QD; 10 consecutive days) effectively inhibits MALT1 protease activity, resulting in a gradual reduction in the frequency of Foxp3+CD25+ Treg cells among circulating CD4+ T cells, with maximal suppression observed after 7 days of treatment. Discontinuation of MLT-943 treatment after day 10 leads to a progressive return of Treg frequency to baseline levels within 4 days. Suboptimal doses of MLT-943 (0.1 and 0.5 mg/kg QD; pO.) do not affect Treg frequency[1].
MLT-943 (oral gavage; 0, 5, 20 or 80 mg/kg/day; 4-13 weeks) induces a decrease in Treg and an increase in total T cell counts across all dose levels. Prolonged treatment for 4 weeks or longer leads to severe immune-mediated pathology in multiple organs, with clinical onset typically observed around week 9 in rats[1].
MLT-943 (pO. admistration; 3 mg/kg; single dose) demonstrates favorable pharmacokinetic parametersin vivo. The Cmax values are 0.7 nM and 0.5 nM in rats and mice, respectively. Additionally, the bioavailability percentages are 86% and 50% in rats and mice, respectively[1].
体外研究
MLT-943 demonstrates high potency and selectivity in vitro. It inhibits stimulated IL-2 secretion in PBMC or whole blood with consistent IC50 values across species (0.07-0.09 μM in PBMC, 0.6-0.8 μM in whole blood)[1].
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