| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
| Targets |
MALT1 protease[1][2][3]
MALT1 (Mucosa-associated lymphoid tissue lymphoma translocation protein 1). Safimaltib is a Class I, specific, allosteric MALT1 protease inhibitor. By binding to MALT1, it blocks its ability to cleave substrates (e.g., BCL10), thereby suppressing the constitutive and antigen-induced activation of the NF-kappaB pathway in malignant B-cells. |
|---|---|
| ln Vitro |
In both mouse and rat tumors, safimaltib (JNJ-67856633) is efficient and highly bioavailable, sometimes resulting in tumor stasis. According to serum IL10 levels or uncleaved BCL10 levels in tumors, safimaltib produced a strong in vivo pharmacodynamic shutdown in both CD79b- and CARD11-mutant ABC-models of DLBCL [1][3].
Safimaltib potently inhibits MALT1 protease activity in biochemical assays, demonstrating high selectivity over other proteases. In cellular assays, it inhibits the proliferation of activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) cell lines that harbor CD79b or CARD11 mutations. Importantly, it is also effective in models that mimic resistance to covalent BTK inhibitors, suggesting a distinct mechanism of action. |
| ln Vivo |
JNJ-67856633 administration was associated with a dose-dependent decrease of Tregs (CD4+CD25+FoxP3+) generation following CD3/28 activation, which shows that MALT1 inhibition may have an immunomodulatory effect [3].
In vivo, Safimaltib is orally active and has been shown to cause tumor stasis (stop in tumor growth) in some preclinical models of B-cell malignancies. By allosterically inhibiting MALT1, the compound suppresses the oncogenic NF-kappaB signaling in the tumor microenvironment, reducing tumor cell proliferation and survival. It is currently in development for hematological cancers, including CLL. |
| Enzyme Assay |
For biochemical MALT1 inhibition assays, purified recombinant MALT1 is incubated with a fluorogenic peptide substrate (e.g., Ac-LRSR-AMC) in an assay buffer. Safimaltib is added at varying concentrations (1-1000 nM). The reaction is monitored kinetically (Ex 380 nm / Em 460 nm), and the IC50 is calculated from the dose-response curve to confirm enzymatic inhibition.
|
| Cell Assay |
For cell-based anti-proliferation assays, ABC-DLBCL cells (e.g., HBL1, TMD8) or CLL cells are seeded in 96-well plates. Safimaltib is added at concentrations ranging from 10 nM to 10 uM. Cell viability and proliferation are assessed after 72-96 hours using CellTiter-Glo or MTT assays. PD analysis includes Western blotting for the cleavage of MALT1 substrates (e.g., BCL10, HOIL-1) and the phosphorylation of NF-kappaB pathway proteins (e.g., IkappaBalpha, p65).
|
| Animal Protocol |
For efficacy studies, Safimaltib is formulated in a suitable vehicle (e.g., 20% hydroxypropyl-beta-cyclodextrin in water) and administered orally to mice bearing ABC-DLBCL or CLL xenografts. Dosing is typically once or twice daily. Tumor volume is measured bi-weekly. At the study endpoint, tumors are harvested for analysis of MALT1 substrate cleavage, NF-kappaB gene signature expression (by qPCR), and proliferation markers (Ki-67 by IHC). Blood is collected for PK and PD biomarker analysis.
|
| ADME/Pharmacokinetics |
Safimaltib is orally bioavailable with a molecular weight of 467.32 g/mol. It is a small-molecule inhibitor with favorable solubility and stability properties. Detailed pharmacokinetic parameters (half-life, Cmax, AUC) are available in preclinical reports but not fully detailed here. For in vivo use, it is typically formulated in aqueous-based vehicles. The compound is stored as a powder at -20degC.
|
| Toxicity/Toxicokinetics |
Safimaltib has undergone preclinical toxicology studies typical for a drug candidate in development. As a MALT1 inhibitor targeting the immune system, potential class-related adverse events may include immune dysregulation, gastrointestinal disturbances, or opportunistic infections. However, these data are not fully detailed in the provided supplier literature. The compound is for research use and is not yet approved for clinical use.
|
| References | |
| Additional Infomation |
Safilmatinib is an orally bioavailable inhibitor of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) with potential antitumor activity. After administration, safilmatinib targets and binds to MALT1, inhibiting its activity. This inhibits the MALT1-dependent signaling pathway, reduces interleukin-10 (IL-10) levels, and upregulates interferon (IFN) levels. Ultimately, this leads to inhibition of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) and nuclear factor-κB (NF-κB) signaling pathways, inducing apoptosis and inhibiting the growth of MALT1-expressing tumor cells. MALT1 belongs to the caspase family and is the active component of the CARD11-BCL10-MALT1 (CBM) signaling complex. It plays an important role in B cell and T cell activation and is overactivated in some tumor cells.
Safimaltib (JNJ-67856633) was developed by Janssen (Johnson & Johnson). It represents a novel therapeutic approach for B-cell malignancies, particularly those resistant to approved BTK inhibitors like ibrutinib. By inhibiting MALT1, it targets the CBM signalosome complex (CARD11-BCL10-MALT1), which is a convergent point for upstream activating mutations. It is not an FDA-approved drug and is in clinical or late-stage preclinical development. |
| Molecular Formula |
C20H11F6N5O2
|
|---|---|
| Molecular Weight |
467.324064493179
|
| Exact Mass |
467.081
|
| CAS # |
2230273-76-2
|
| PubChem CID |
134609793
|
| Appearance |
Off-white to yellow solid powder
|
| LogP |
2.9
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
33
|
| Complexity |
788
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
FC(C1=C(C(NC2C=CN=C(C(F)(F)F)C=2)=O)C=NN1C1=CC=CC2C(NC=CC1=2)=O)(F)F
|
| InChi Key |
APWRZPQBPCAXFP-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H11F6N5O2/c21-19(22,23)15-8-10(4-6-27-15)30-18(33)13-9-29-31(16(13)20(24,25)26)14-3-1-2-12-11(14)5-7-28-17(12)32/h1-9H,(H,28,32)(H,27,30,33)
|
| Chemical Name |
1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 125 mg/mL (267.48 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.45 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 (4.45 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. 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 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1399 mL | 10.6993 mL | 21.3986 mL | |
| 5 mM | 0.4280 mL | 2.1399 mL | 4.2797 mL | |
| 10 mM | 0.2140 mL | 1.0699 mL | 2.1399 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.
Link: https://clinicaltrials.gov/ct2/show/NCT06788509
Conditions:Leukemia, Myeloid, Acute|Leukemia, Lymphocytic, Chronic, B-Cell|Lymphoma, Non-Hodgkin|Myelodysplastic Syndromes|Neoplasms|Solid Tumor, Adult|Prostatic Neoplasms, Castration-ResistantLink: https://clinicaltrials.gov/ct2/show/NCT04876092
Conditions:Leukemia, Lymphocytic, Chronic, B-Cell|Lymphoma, Non-HodgkinLink: https://clinicaltrials.gov/ct2/show/NCT04657224
Conditions:Lymphoma, Non-Hodgkin|Chronic Lymphocytic Leukemia
Title:A Study of JNJ-67856633 in Participants With Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)
Status:Completed
updateDate:2025-06-22
Ctid:NCT03900598
Link: https://clinicaltrials.gov/ct2/show/NCT03900598
Conditions:Leukemia, Lymphocytic, Chronic, B-Cell|Lymphoma, Non-HodgkinProducts are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
