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MLT-943 is a potent, selective and orally active MALT1 protease inhibitor. MLT-943 inhibits stimulated-IL-2 secretion in PBMC or in whole blood with a similar IC 50 across species (0.07-0.09 μM in PBMC, 0.6-0.8 μM in whole blood). MLT-943 has anti-inflammatory activities and can be used for FcgR-mediated inflammation research.
In Vitro
MLT-943 shows a high potency and selectivity in vitro.?MLT-943 inhibits stimulated IL-2 secretion in PBMC or in whole blood with a similar IC 50 across species (0.07-0.09 μM in PBMC, 0.6-0.8 μM in whole blood). MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
MLT-943 (oral gavage; 10 mg/kg; QD) prophylactic treatment in the rat collagen-induced arthritis model suppresses anti-collagen antibody production, fully prevents paw swelling, and normalizes joint histology scores?in rat model . MLT-943 (oral gavage; 5 mg/kg; QD; 10 consecutive days) effectively inhibits MALT1 protease activity and results in a progressive reduction in the frequency of Foxp 3+ CD25 + ?Treg cells in circulating CD4 + ?T cells, which was maximal after 7 days of treatment. And Discontinuation of MLT-943 treatment after day 10 leads to Treg frequency progressively returning to their original values within 4 days. Suboptimal doses of MLT-943 (0.1 and 0.5 mg/kg QD; p.o.) does not impact the Treg frequency . MLT-943 (oral gavage; 0, 5, 20 or 80 mg/kg/day; 4-13 weeks) causes a reduction in Treg and an increase in total T cell counts, in both 4- and 13-week rat toxicity studies at all dose levels. While a 4-Longer treatment induces severe immune-mediated pathology in multiple organs, with clinical onset starting around week 9 in rat . MLT-943 (p.o. admistration; 3 mg/kg; single dose) exhibits a good PK parameters in vivo . The C max values are 0.7 nM and 0.5 nM, respectively in rat and mice, respectively. And the F% are 86% and 50% in rat and mice, respective . For i.v. admistration the compound is formed in NMP:PEG200 (30/70); For p.o. admistration solution is formed in MC:Tween 80:Water (0.5:0.5:99) solution (Sourced from literature, for reference only) . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Naïve rats Dosage: 5 mg/kg Administration: Oral gavage; 5 mg/kg, 10 consecutive days or 0.1 mg/kg MLT-943 Result: Induced a severe immune-mediated pathology after a prolonged treatment
Form:Solid
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| Solubilidade | DMSO : 250 mg/mL (602.74 mM; Need ultrasonic) |
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