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| Targets |
The primary target of MLT-747 is MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1), a paracaspase that plays a critical role in immune receptor signaling, particularly in the NF-kappaB pathway. MLT-747 acts as an allosteric inhibitor, binding to MALT1 in the allosteric Trp580 pocket. By inhibiting MALT1 activity, the compound modulates downstream signaling pathways involved in lymphocyte activation, proliferation, and survival. MALT1 is a validated therapeutic target for certain lymphomas and autoimmune diseases, making MLT-747 a valuable tool for studying these conditions.
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| ln Vitro |
MLT-747 (0–20 μM) stabilizes MALT1–W580S cells, exhibiting an EC50 of 314 nM [1].
In vitro studies demonstrate that MLT-747 is a potent inhibitor of MALT1 with an IC₅0 of 14 nM. The compound (0-20 microM) stabilizes cellular MALT1-W580S with an EC₅0 of 314 nM. MLT-747 is a selective, allosteric inhibitor that binds to MALT1 in the Trp580 pocket. Its potent inhibitory activity makes it a valuable tool for studying MALT1-dependent signaling pathways and for validating MALT1 as a therapeutic target in lymphomas and autoimmune diseases. The compound's effects on MALT1 activity can be assessed in various cell-based and biochemical assays. |
| ln Vivo |
In vivo studies of MLT-747 are likely focused on evaluating its efficacy in animal models of MALT1-dependent diseases, such as lymphomas and autoimmune disorders. As a potent and selective allosteric inhibitor of MALT1 with an IC₅0 of 14 nM, the compound is expected to demonstrate significant therapeutic effects in vivo. MLT-747 may be used to study the role of MALT1 in immune signaling and to validate MALT1 as a therapeutic target. Further in vivo studies are needed to fully characterize its pharmacokinetic properties, bioavailability, and efficacy in various disease models.
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| Enzyme Assay |
For in vitro enzyme/receptor binding assays, MLT-747 can be evaluated using biochemical assays that measure MALT1 paracaspase activity. The compound is incubated with recombinant MALT1 enzyme and a suitable peptide substrate at various concentrations. MALT1-mediated cleavage of the substrate is quantified using fluorometric or colorimetric methods. IC₅0 values are determined from dose-response curves. Binding affinity to the allosteric Trp580 pocket can be assessed using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). Selectivity profiling against other proteases may be performed to confirm specificity.
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| Cell Assay |
For in vitro cellular experiments, MLT-747 is tested in cell lines expressing MALT1, such as lymphoma cell lines or primary lymphocytes. Cells are cultured in appropriate media and treated with various concentrations of the compound (typically ranging from nanomolar to micromolar). MALT1 activity is assessed by measuring the cleavage of MALT1 substrates using Western blotting or other detection methods. NF-kappaB signaling and downstream gene expression are evaluated by qPCR or reporter assays. Cell viability, proliferation, and apoptosis are assessed using standard assays. The compound's effects on MALT1-W580S stabilization are measured.
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| Animal Protocol |
For in vivo animal experiments, MLT-747 can be administered to mice via various routes including oral gavage, intravenous injection, or intraperitoneal injection, depending on its solubility and pharmacokinetic properties. The compound's efficacy can be evaluated in xenograft models of MALT1-dependent lymphomas or in autoimmune disease models. Typical dosing regimens may range from 1 to 50 mg/kg administered daily or intermittently. Tumor volume, disease progression, and immune cell activation are monitored. Pharmacodynamic markers such as MALT1 substrate cleavage and NF-kappaB target gene expression are measured in tissues.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of MLT-747 are not extensively detailed in the public literature. As a small molecule with a molecular weight of 478.33 g/mol, it may have reasonable oral bioavailability and tissue distribution. The presence of chlorine atoms may influence its metabolic stability and clearance. Detailed parameters such as Cₘₐₓ, Tₘₐₓ, AUC, half-life, and clearance would need to be determined through comprehensive PK studies. The compound's protein binding, metabolism, and excretion pathways remain to be fully characterized. Formulation development may be necessary for optimal in vivo administration.
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| Toxicity/Toxicokinetics |
Toxicological data for MLT-747 are limited, as it is primarily a research tool. As a MALT1 inhibitor, its toxicity would depend on the importance of MALT1 for normal immune function. MALT1 plays a critical role in lymphocyte activation and proliferation, and its inhibition could have immunosuppressive effects. Comprehensive toxicology studies including acute and repeated-dose toxicity, genotoxicity, and cardiotoxicity assessments would be needed for further development. Appropriate safety precautions should be taken when handling this compound, including the use of personal protective equipment and adherence to institutional safety guidelines.
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| References | |
| Additional Infomation |
MLT-747 is a research compound used to study MALT1 biology and evaluate MALT1 as a therapeutic target. No clinical trials or regulatory approvals have been reported for this compound as a therapeutic agent. It is available from various chemical suppliers for research purposes only. The compound is a potent, selective, allosteric inhibitor of MALT1 with an IC₅0 of 14 nM that binds in the Trp580 pocket. MLT-747 stabilizes cellular MALT1-W580S with an EC₅0 of 314 nM and is a valuable tool for studying MALT1-dependent signaling pathways.
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| Molecular Formula |
C20H21CL2N7O3
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| Molecular Weight |
478.331841230392
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| Exact Mass |
477.108
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| CAS # |
2097853-86-4
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| PubChem CID |
129117094
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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 |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
684
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1=CC(=CN=C1C(N1CCCC1)=O)NC(NC1C=NC2=CC(=NN2C=1[C@H](C)OC)Cl)=O
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| InChi Key |
OJTGJRAKRGEDPI-NSHDSACASA-N
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| InChi Code |
InChI=1S/C20H21Cl2N7O3/c1-11(32-2)18-14(10-23-16-8-15(22)27-29(16)18)26-20(31)25-12-7-13(21)17(24-9-12)19(30)28-5-3-4-6-28/h7-11H,3-6H2,1-2H3,(H2,25,26,31)/t11-/m0/s1
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| Chemical Name |
1-[2-chloro-7-[(1S)-1-methoxyethyl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-[5-chloro-6-(pyrrolidine-1-carbonyl)pyridin-3-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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~100 mg/mL (~209.06 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0906 mL | 10.4530 mL | 20.9061 mL | |
| 5 mM | 0.4181 mL | 2.0906 mL | 4.1812 mL | |
| 10 mM | 0.2091 mL | 1.0453 mL | 2.0906 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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