| 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 |
Purity: =99.66%
| Targets |
IC50: 5 nM (MALT1)[1] Kd: 13 nM (MALT1(329-728)-W580S), 42 nM (MALT1(329-728))[1]
MLT-748 targets MALT1, a paracaspase that functions as a key signaling mediator in the NF-κB pathway downstream of antigen receptor engagement. MALT1 has both scaffold and protease functions, cleaving specific substrates to promote NF-κB activation, which is essential for lymphocyte activation, proliferation, and survival. MLT-748 binds allosterically to the Trp580 pocket, stabilizing the inactive conformation of the catalytic site. By inhibiting MALT1 protease activity, MLT-748 blocks substrate cleavage and NF-κB signaling in B and T cells. |
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| ln Vitro |
With the same affinity as wild-type MALT1 (329-728) (Kd, 42 nM), MLT-748 reversibly binds the human mutant MALT1 (329-728)-W580S (Kd, 13 nM) [1]. MALT1-W580S cells, EC50 69 nM, are stabilized by MLT-748 (0-2 μM)[1]. MLT-748 (2 μM, 24 hours) phosphorylates IκBα and p65 in immortalized B cells from MALT1mut/mut patients [1].
In vitro, MLT-748 demonstrates potent inhibition of MALT1 with an IC50 of 5 nM. The compound binds selectively to the allosteric Trp580 pocket and locks the catalytic site in an inactive state. MLT-748 blocks the cleavage of MALT1 substrates in B and T cells. The compound shows concentration-dependent inhibition of MALT1 activity in biochemical assays using purified enzyme preparations. In cellular models, MLT-748 inhibits NF-κB signaling and downstream gene expression. |
| ln Vivo |
In vivo activity data for MLT-748 are limited, as the compound is primarily studied in vitro. Based on its MALT1 inhibitory mechanism, the compound is expected to modulate immune responses and exhibit anti-tumor activity in animal models of B-cell malignancies and autoimmune diseases. However, detailed efficacy studies in animal models have not been extensively reported. The compound's potential for in vivo applications requires further investigation.
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| Enzyme Assay |
The in vitro enzyme inhibition assay for MLT-748 typically involves measuring MALT1 protease activity using a fluorogenic peptide substrate. Purified recombinant human MALT1 is incubated with varying concentrations of MLT-748 (0.001-1000 nM) in assay buffer at 37°C for 30-60 minutes. The reaction is initiated by adding the substrate, and fluorescence is measured continuously. IC50 values are calculated from dose-response curves. Binding affinity is determined by surface plasmon resonance or other biophysical methods.
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| Cell Assay |
Western Blot Analysis
Cell Types: MALT1mut/mut patient immortalized B cells Tested Concentrations: 2 µM Incubation Duration: 24 hrs (hours) Experimental Results: Increased NF-κB signaling phosphorylation of both p65 and IκBα as early as 5 min after stimulation with PMA and ionomycin. For in vitro cell-based assays, B or T lymphocytes are cultured and treated with MLT-748 at concentrations ranging from 0.1-100 µM for 4-24 hours. MALT1 activity is measured in cell lysates using a protease activity assay. NF-κB signaling is assessed by measuring phosphorylation of IκBα or nuclear translocation of NF-κB. Cytokine production (e.g., IL-2, IL-6) is measured by ELISA. Cell proliferation is assessed by MTT or [³H]-thymidine incorporation assays. |
| Animal Protocol |
In vivo animal studies for MLT-748 have not been extensively reported. Based on the compound's mechanism as a MALT1 inhibitor, potential in vivo studies would involve administration to mouse models of B-cell lymphoma, autoimmune disease, or inflammatory conditions via oral gavage or intraperitoneal injection at doses ranging from 1-50 mg/kg. NF-κB signaling and immune cell activation would be assessed in tissues. Tumor growth or disease progression would be monitored.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of MLT-748 have been partially characterized. The molecular weight is 492.32 g/mol. The compound is soluble in DMSO at 98 mg/mL (199.05 mM). For in vivo administration, formulations such as 5% DMSO, 40% PEG300, 5% Tween 80, and 50% ddH₂O or CMC-Na suspensions have been validated. Detailed pharmacokinetic parameters such as bioavailability and half-life have not been extensively reported.
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| Toxicity/Toxicokinetics |
Toxicology data for MLT-748 are limited. As a research compound, it has not been systematically evaluated for safety. The compound's mechanism of MALT1 inhibition suggests potential effects on immune function, which would require careful safety assessment. Standard toxicological endpoints including body weight, organ weights, clinical chemistry, and histopathology should be evaluated. The compound is intended for research use only and is not approved for human use.
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| References | |
| Additional Infomation |
MLT-748 is a potent and selective allosteric inhibitor of MALT1 with an IC50 of 5 nM. It binds to the Trp580 pocket and locks the catalytic site in an inactive state. The compound blocks MALT1 substrate cleavage and NF-κB signaling in B and T cells. MLT-748 is a valuable research tool for studying MALT1 function, NF-κB signaling, and immune regulation. It is intended for research use only and is not approved for therapeutic applications.
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| Molecular Formula |
C19H19CL2N9O3
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|---|---|
| Molecular Weight |
492.318660020828
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| Exact Mass |
491.098
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| CAS # |
1832578-30-9
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| PubChem CID |
129072285
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| Appearance |
White to off-white solid powder
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| LogP |
1.7
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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 |
7
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| Heavy Atom Count |
33
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| Complexity |
662
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| Defined Atom Stereocenter Count |
2
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| SMILES |
ClC1C=C2N=CC(=C([C@H]([C@@H](C)OC)OC)N2N=1)NC(NC1C=NC(=C(C=1)Cl)N1N=CC=N1)=O
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| InChi Key |
XKQLNDPUQSZBJW-QGHHPUGFSA-N
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| InChi Code |
InChI=1S/C19H19Cl2N9O3/c1-10(32-2)17(33-3)16-13(9-22-15-7-14(21)28-29(15)16)27-19(31)26-11-6-12(20)18(23-8-11)30-24-4-5-25-30/h4-10,17H,1-3H3,(H2,26,27,31)/t10-,17+/m1/s1
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| Chemical Name |
1-[2-chloro-7-[(1R,2R)-1,2-dimethoxypropyl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-[5-chloro-6-(triazol-2-yl)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 |
| 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: 200 mg/mL (406.24 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.08 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.22 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.22 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.08 mg/mL (4.22 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. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0312 mL | 10.1560 mL | 20.3120 mL | |
| 5 mM | 0.4062 mL | 2.0312 mL | 4.0624 mL | |
| 10 mM | 0.2031 mL | 1.0156 mL | 2.0312 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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