| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
MALT1 (Mucosa-associated lymphoid tissue lymphoma translocation protein 1). MLT-231 is a specific allosteric inhibitor of the MALT1 protease. It binds to the MALT1 paracaspase domain, blocking its ability to cleave endogenous substrates such as BCL10, thereby preventing the activation of the NF-kappaB pathway.
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| ln Vitro |
MLT-231 (19.5–10,000 nM) prevents OCI-Ly3 cells from proliferating. MLT-231 (50-5000 nM; 24 hours) suppresses the expression of the NF-κB target gene IRF4 while causing the uncleaved forms of its substrates, CYLD, BCL10, and RELB, to accumulate[1].
MLT-231 is a highly potent MALT1 inhibitor with an IC50 of 9 nM in biochemical assays. It selectively inhibits the cleavage of the endogenous substrate BCL10 in cells with an IC50 of 160 nM. This inhibition is specific and allosteric, meaning it binds to a regulatory site on the enzyme rather than the active site, leading to high selectivity over other caspases and proteases, thereby minimizing off-target effects. |
| ln Vivo |
In the ABC-DLBCL xenograft model, MLT-231 (10-100 mg/kg; po; bid schedule for 2 weeks) exhibits in vivo efficacy[1]. Following IV administration of MLT-231 (1 mg/kg) to BALB/c mice, the CL, t1/2, and Vss are, respectively, 11 mL/min/kg, 1.9 hours, and 1.5 L/kg[1]. Following intravenous administration of MLT-231 (1 mg/kg) to Sprague-Dawley rats, the CL, t1/2, and Vss are 41 mL/min/kg, 3.2 hours, and 9.4 L/kg, respectively[1]. The AUC0-24, Cmax, and F values for MLT-231 (3 mg/kg; po; BALB/c mice) are 3096 nM/h, 549 nM, and 99%, respectively[1]. The AUC0-24, Cmax, and F values for MLT-231 (3 mg/kg; po; Sprague-Dawley rats) are 547 nM/h, 46 nM, and 61%, correspondingly.
In vivo, MLT-231 has demonstrated anti-cancer effects in ABC-DLBCL (activated B-cell-like diffuse large B-cell lymphoma) xenograft models. By allosterically inhibiting MALT1, the compound suppresses the constitutive NF-kappaB signaling that drives the survival and proliferation of ABC-DLBCL cells, leading to tumor growth inhibition or regression. This validates MALT1 as a therapeutic target in these lymphomas. |
| Enzyme Assay |
For biochemical MALT1 inhibition assays, purified recombinant MALT1 paracaspase domain is incubated with a fluorogenic peptide substrate (e.g., Ac-LRSR-AMC). MLT-231 is added at varying concentrations (0.1-1000 nM). The reaction is initiated, and the release of AMC is monitored continuously (Ex 380 nm / Em 460 nm). IC50 values are calculated from the dose-response curves to confirm potency (9 nM).
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: OCI-Ly3 cells Tested Concentrations: 50-5000 nM Incubation Duration: 24 hrs (hours) Experimental Results: NF-κB target gene IRF4 was suppressed. For cellular mechanism-of-action (MOA) studies, ABC-DLBCL cell lines (e.g., TMD8, HBL1) are treated with MLT-231 (10-1000 nM) for 6-24 hours. Cells are lysed, and the cleavage of endogenous MALT1 substrates (e.g., BCL10, HOIL-1) is analyzed by Western blot. NF-kappaB pathway activation is assessed by measuring the phosphorylation and degradation of IkappaBalpha and the nuclear translocation of p65 by immunofluorescence or Western blot. |
| Animal Protocol |
Animal/Disease Models: Scid-beige mice (OCI-Ly10 ABC-DLBCL type xenograft model)[1]
Doses: 10, 30, and 100 mg/kg Route of Administration: Po; bid schedule for 2 weeks Experimental Results: Led to tumor stasis, while being well tolerated. For efficacy studies, MLT-231 is typically formulated in a vehicle such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline. It is administered orally or intraperitoneally to mice bearing subcutaneous ABC-DLBCL xenografts (e.g., TMD8 cells). Doses are optimized based on PK/PD studies. Tumor volume is measured bi-weekly. At study termination, tumors are harvested for analysis of MALT1 substrate cleavage (BCL10) and NF-kappaB activation by Western blot and immunohistochemistry. |
| ADME/Pharmacokinetics |
MLT-231 has a molecular weight of 469.85 g/mol and a molecular formula of C19H19ClF3N7O2. It is a solid powder with high solubility in DMSO. Pharmacokinetic parameters are not detailed in the provided results, but as an allosteric inhibitor, it is expected to have favorable oral bioavailability and a half-life suitable for in vivo efficacy studies. It should be stored at -20degC, protected from light and moisture.
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| Toxicity/Toxicokinetics |
Toxicological data for MLT-231 are limited to preclinical study reports. In ABC-DLBCL xenograft models at efficacious doses, no significant systemic toxicity or body weight loss was reported, suggesting a favorable therapeutic index. However, as with any MALT1 inhibitor, there is a potential risk of immunosuppression or gastrointestinal toxicity due to the role of MALT1 in normal immune function. Standard handling precautions for research chemicals should be used.
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| References | |
| Additional Infomation |
MLT-231 is a highly selective allosteric MALT1 inhibitor developed by Merck (EMD Serono). It is distinct from MLT-943 as it binds to an allosteric pocket (Trp580), offering potentially better selectivity. It is a research-grade chemical and is not an FDA-approved drug. It is used to study the therapeutic potential of MALT1 inhibition in genetically defined subtypes of diffuse large B-cell lymphoma (DLBCL) and other NF-kappaB-driven malignancies.
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| Molecular Formula |
C19H19CLF3N7O2
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| Molecular Weight |
469.848072290421
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| Exact Mass |
469.124
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| CAS # |
2682102-10-7
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| PubChem CID |
146680905
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| Appearance |
White to off-white solid powder
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
32
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| Complexity |
665
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@H]1COC[C@@H](N1C2=C(C=NC3=CC(=NN32)Cl)NC(=O)NC4=CC(=NC=C4)C(F)(F)F)C
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| InChi Key |
BFPCFGGFGQMJQG-QWRGUYRKSA-N
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| InChi Code |
InChI=1S/C19H19ClF3N7O2/c1-10-8-32-9-11(2)29(10)17-13(7-25-16-6-15(20)28-30(16)17)27-18(31)26-12-3-4-24-14(5-12)19(21,22)23/h3-7,10-11H,8-9H2,1-2H3,(H2,24,26,27,31)/t10-,11-/m0/s1
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| Chemical Name |
1-[2-chloro-7-[(3S,5S)-3,5-dimethylmorpholin-4-yl]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: 110 mg/mL (234.12 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6 mg/mL (12.77 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 60.0 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: ≥ 5.5 mg/mL (11.71 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 55.0 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 | 2.1283 mL | 10.6417 mL | 21.2834 mL | |
| 5 mM | 0.4257 mL | 2.1283 mL | 4.2567 mL | |
| 10 mM | 0.2128 mL | 1.0642 mL | 2.1283 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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