| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| ln Vitro |
In vitro, MLT-943 exhibits strong potency and selectivity. With comparable cross-species IC50s (0.07-0.09 μM in PBMC and 0.6-0.8 μM in whole blood), MLT-943 suppresses stimulated IL-2 secretion in both PBMC and whole blood [1].
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| ln Vivo |
In a rat model of collagen-induced arthritis, prophylactic administration of MLT-943 (oral gavage; 10 mg/kg; QD) inhibits the generation of anti-collagen antibodies, completely prevents paw swelling, and enhances joint stability in the rat model. Scores based on histology were normalized[1]. MLT-943 (oral gavage; 5 mg/kg; QD; 10 days) reaches a maximum after 7 days of treatment and efficiently decreases MALT1 protease activity as well as the frequency of Foxp3+CD25+ Treg cells in circulating CD4+ T cells. After stopping MLT-943 treatment on day 10, Treg frequencies took four days to progressively recover to their initial levels. Treg frequency remained unaffected by suboptimal dosages of MLT-943 (0.1 and 0.5 mg/kg QD; po)[1]. In 4- and 13-week rat toxicity trials, MLT-943 (oral gavage; 0, 5, 20, or 80 mg/kg/day; 4–13 weeks) led to decreased Treg and total T cell counts at all treatment levels. Rats have a clinical onset of about 9 weeks, despite the fact that 4-Longer therapy promotes significant immune-mediated disease in several organs[1]. In vivo, MLT-943 (oral administration; 3 mg/kg; single dosage) shows positive PK characteristics. Rats and mice have Cmax values of 0.7 nM and 0.5 nM, respectively. Rats and mice have F%s of 86% and 50%, respectively[1]. Note: MC:Tween 80:Water (0.5:0.5:99) solution (from the literature, for reference only) is the solvent for oral administration, and NMP:PEG200 (30/70) solution is the solvent for intravenous administration[1].
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| Animal Protocol |
Animal/Disease Models: Naïve rats[1]
Doses: 5 mg/kg Route of Administration: Oral gavage; 5 mg/kg, 10 days or 0.1 mg/kg MLT-943 Experimental Results: Induced a severe immune-mediated pathology after a prolonged treatment |
| References |
[1]. Kea Martin, et al. Pharmacological Inhibition of MALT1 Protease Leads to a Progressive IPEX-Like Pathology. Front Immunol
[2]. Jean Quancard, et al. Optimization of the In Vivo Potency of Pyrazolopyrimidine MALT1 Protease Inhibitors by Reducing Metabolism and Increasing Potency in Whole Blood. J Med Chem. 2020 Dec 10;63(23):14594-14608. |
| Molecular Formula |
C16H14CLF3N6O2
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|---|---|
| Molecular Weight |
414.77
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| CAS # |
1832576-04-1
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| SMILES |
ClC1C([H])=C2N=C([H])C(=C([C@]([H])(C([H])([H])[H])OC([H])([H])[H])N2N=1)N([H])C(N([H])C1C([H])=C([H])N=C(C(F)(F)F)C=1[H])=O
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Solubility (In Vitro) |
DMSO: 250 mg/mL (602.74 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.01 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.01 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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