MLT-943 是一种有效的、选择性的、口服活性的MALT1 protease抑制剂。MLT-943 可抑制 PBMC 或全血中 IL-2 的分泌,PBMC 中抑制的IC50值为 0.07~0.09 μM,全血中抑制的IC50值为 0.6~0.8 μM)。MLT-943具有抗炎活性,可用于 FcgR 介导的炎症研究。
生物活性 | MLT-943 is a potent, selective and orally activeMALT1proteaseinhibitor. MLT-943 inhibits stimulated-IL-2 secretion in PBMC or in whole blood with a similarIC50 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[1]. |
体外研究 (In Vitro) | MLT-943 shows a high potency and selectivityin vitro. MLT-943 inhibits stimulated IL-2 secretion in PBMC or in whole blood with a similar IC50across species (0.07-0.09 μM in PBMC, 0.6-0.8 μM in whole blood)[1].
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体内研究 (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[1]. 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 Foxp3+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[1]. 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[1]. MLT-943 (p.o. admistration; 3 mg/kg; single dose) exhibits a good PK parametersin vivo. The Cmaxvalues 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[1]. 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)[1].
Animal Model: | Naive rats[1] | 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 |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : 250 mg/mL(602.74 mM;Need ultrasonic) 配制储备液 1 mM | 2.4110 mL | 12.0549 mL | 24.1097 mL | 5 mM | 0.4822 mL | 2.4110 mL | 4.8219 mL | 10 mM | 0.2411 mL | 1.2055 mL | 2.4110 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (5.01 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.01 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (5.01 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.01 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。
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