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| Targets |
MALT1 (Mucosa-associated lymphoid tissue lymphoma translocation protein 1). MLT-985 is a selective allosteric inhibitor of MALT1. It binds to the MALT1 paracaspase domain, blocking its ability to cleave endogenous substrates like BCL10, thereby preventing the activation of the NF-kappaB pathway, a key driver of inflammation and B-cell survival.
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| ln Vitro |
MLT-985 is a highly potent and selective MALT1 inhibitor with a biochemical IC50 of 3 nM. In the cellular environment, it suppresses aberrant CARD11/BCL10/MALT1 complex signaling with an EC50 of approximately 20 nM in an IL-2 reporter gene assay using Jurkat T-cells. By blocking MALT1 protease activity, it effectively suppresses cell proliferation driven by constitutive NF-kappaB activation in B-cell malignancies.
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| ln Vivo |
MLT-985 is orally active and has demonstrated efficacy in preclinical models of NF-kappaB-driven cancers. By inhibiting MALT1, it suppresses cell growth and intervenes in aberrant signaling associated with the CARD11/BCL10/MALT1 complex. Detailed in vivo study results are not provided in the current search excerpts, but as a potent member of the MLT series, it is expected to cause tumor stasis or regression in B-cell lymphoma xenograft models.
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| Enzyme Assay |
For biochemical MALT1 inhibition assays, purified recombinant MALT1 paracaspase is incubated with a fluorogenic peptide substrate (e.g., Ac-LRSR-AMC) in a reaction buffer. MLT-985 is added at varying concentrations (0.1-1000 nM). The reaction is initiated, and the release of AMC is monitored kinetically (Ex 380 nm / Em 460 nm) to calculate the IC50 (3 nM).
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| Cell Assay |
For cellular signaling assays, ABC-DLBCL cells (e.g., TMD8, HBL1) or Jurkat T-cells are treated with MLT-985 (1-100 nM) for 6-24 hours. The cells are lysed, and the inhibition of MALT1 activity is verified by Western blot analysis of the cleavage of the endogenous substrate BCL10. NF-kappaB pathway suppression is assessed by measuring the phosphorylation and degradation of IkappaBalpha and the phosphorylation of p65.
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| Animal Protocol |
For efficacy studies, MLT-985 is typically formulated in a vehicle such as 0.5% methylcellulose or a mixture of 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline. It is administered orally to mice bearing subcutaneous ABC-DLBCL xenografts (e.g., TMD8 or OCI-Ly10 cells). Doses are optimized based on PK/PD modeling. Tumor volume is measured bi-weekly. At the end of the study, tumors are harvested for histology and Western blotting to confirm target engagement (BCL10 cleavage).
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| ADME/Pharmacokinetics |
MLT-985 is a small molecule with a molecular weight of 448.27 g/mol and a molecular formula of C17H15Cl2N9O2. It is soluble in DMSO and is provided as a solid powder. It is recommended to store the compound at -20degC, protected from light and moisture. Pharmacokinetic data are not detailed in the provided results, but as an orally active compound, it is expected to have a favorable profile for in vivo studies.
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| Toxicity/Toxicokinetics |
Toxicological data for MLT-985 are not detailed in the provided search results. In preclinical xenograft studies at efficacious doses, the compound is generally well-tolerated, with no significant body weight loss or acute toxicity reported. Standard laboratory safety precautions should be observed when handling this research chemical. It is not intended for human consumption. The high selectivity of this allosteric inhibitor suggests a lower risk of off-target toxicity.
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| References | |
| Additional Infomation |
MLT-985 is a research-grade chemical developed by Merck (EMD Serono). It is not an FDA-approved drug. It is a valuable tool for studying the role of the CARD11-BCL10-MALT1 (CBM) signalosome in normal B-cell and T-cell development and function, as well as its pathological role in autoimmune diseases and B-cell lymphomas (ABC-DLBCL). It is utilized to validate MALT1 as a therapeutic target.
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| Molecular Formula |
C17H15CL2N9O2
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| Molecular Weight |
448.27
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| Exact Mass |
447.072
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| CAS # |
1832576-25-6
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| Related CAS # |
(R)-MLT-985;1832577-07-7
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| PubChem CID |
129072335
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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 |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
600
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| Defined Atom Stereocenter Count |
1
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| SMILES |
N(C1=C([C@@H](OC)C)N2N=C(Cl)C=C2N=C1)C(NC1=CC(Cl)=C(N2N=CC=N2)N=C1)=O
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| InChi Key |
GBIASRXDYFFUED-VIFPVBQESA-N
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| InChi Code |
InChI=1S/C17H15Cl2N9O2/c1-9(30-2)15-12(8-20-14-6-13(19)26-27(14)15)25-17(29)24-10-5-11(18)16(21-7-10)28-22-3-4-23-28/h3-9H,1-2H3,(H2,24,25,29)/t9-/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-(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: 100 mg/mL (223.08 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 | 2.2308 mL | 11.1540 mL | 22.3080 mL | |
| 5 mM | 0.4462 mL | 2.2308 mL | 4.4616 mL | |
| 10 mM | 0.2231 mL | 1.1154 mL | 2.2308 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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