| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
MALT1 (Mucosa-associated lymphoid tissue lymphoma translocation protein 1). MLT-943 is a selective and potent MALT1 protease inhibitor. It inhibits the paracaspase activity of MALT1, which is required for the cleavage of substrates like BCL10 and the activation of the NF-kappaB pathway, a central regulator of inflammation and immune responses.
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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].
In a cell-free enzymatic assay using a MALT1-specific fluorogenic substrate, MLT-943 inhibits MALT1 protease activity with high potency, demonstrating an IC50 of 40 nM in an IL-2 reporter gene assay in Jurkat T-cells. In cellular assays, it inhibits stimulated IL-2 secretion in human peripheral blood mononuclear cells (PBMCs) with an IC50 of 74 nM. This activity is consistent across species (0.07-0.09 uM in PBMC). |
| 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].
In a rat model of collagen-induced arthritis (CIA), prophylactic oral administration of MLT-943 (10 mg/kg, once daily, QD) was highly effective. It inhibited the generation of anti-collagen antibodies, completely prevented joint swelling, and enhanced joint stability. These results demonstrate that inhibiting MALT1 protease activity is a viable strategy for reducing the severity of autoimmune arthritis. |
| Enzyme Assay |
For cell-free MALT1 protease assays, recombinant human MALT1 is incubated with a fluorogenic peptide substrate (e.g., Ac-LRSR-AMC) in an assay buffer (50 mM Tris-HCl, pH 7.5, 150 mM NaCl). MLT-943 is added at varying concentrations (1-1000 nM). The reaction is initiated, and the release of AMC is monitored kinetically (Ex 380 nm / Em 460 nm) to calculate the IC50.
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| Cell Assay |
For T-cell activation assays, human peripheral blood mononuclear cells (PBMCs) are stimulated with phytohemagglutinin (PHA) or anti-CD3/CD28 antibodies. MLT-943 (10-1000 nM) is added to the culture medium. After 48 hours, supernatant is collected, and IL-2 and IFN-gamma levels are quantified by ELISA. Cell viability is measured using the MTT assay to rule out cytotoxicity, as MLT-943 specifically inhibits activation without killing the cells.
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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 The collagen-induced arthritis (CIA) model is used in rats. MLT-943 is formulated in a suitable vehicle (e.g., 0.5% methylcellulose). Prophylactic administration begins on the day of the first immunization and continues daily (10 mg/kg, oral gavage). Clinical arthritis scores (based on paw swelling) are monitored daily. On the terminal day, blood is collected for anti-collagen antibody measurements (ELISA), and paw tissues are collected for histopathological analysis of inflammation and joint damage. |
| ADME/Pharmacokinetics |
MLT-943 is orally bioavailable. It has a molecular weight of approximately 398.8 g/mol. For in vivo studies, it is typically formulated in a vehicle such as 0.5% methylcellulose or a mixture of DMSO/PEG300/Tween-80/saline. Detailed pharmacokinetic parameters (half-life, Cmax, AUC) are not extensively published in the provided summaries but are consistent with an orally active small molecule. The compound is stored as a powder at -20degC.
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| Toxicity/Toxicokinetics |
Toxicological data for MLT-943 are not fully detailed in the provided literature search results, but the compound is noted for its anti-inflammatory activity and is generally well-tolerated at the doses used in the rat CIA model (10 mg/kg), with no acute toxicity reported. Standard safety precautions for research chemicals should be followed. It is not for human consumption. The selective nature of MALT1 inhibitors offers a potentially safer profile than broad immunosuppressants.
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| References |
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| Additional Infomation |
MLT-943 is a first-generation selective MALT1 inhibitor developed by Merck (EMD Serono). It is a research-grade chemical used to study the role of the CARD11/BCL10/MALT1 (CBM) complex in NF-kappaB signaling and the pathogenesis of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus (SLE). It is not an FDA-approved drug.
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| Molecular Formula |
C16H14CLF3N6O2
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| Molecular Weight |
414.7696
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| Exact Mass |
414.081
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| CAS # |
1832576-04-1
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| PubChem CID |
118540057
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| Appearance |
White to off-white solid powder
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
557
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| Defined Atom Stereocenter Count |
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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| InChi Key |
ZMPUACZRXUZAJD-QMMMGPOBSA-N
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| InChi Code |
InChI=1S/C16H14ClF3N6O2/c1-8(28-2)14-10(7-22-13-6-12(17)25-26(13)14)24-15(27)23-9-3-4-21-11(5-9)16(18,19)20/h3-8H,1-2H3,(H2,21,23,24,27)/t8-/m0/s1
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| Chemical Name |
1-[2-chloro-7-[(1S)-1-methoxyethyl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-[2-(trifluoromethyl)pyridin-4-yl]urea
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| 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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