Physicochemical Properties
| Molecular Formula | C19H19CL2N9O3 |
| Molecular Weight | 492.318660020828 |
| Exact Mass | 491.098 |
| CAS # | 1832578-30-9 |
| PubChem CID | 129072285 |
| Appearance | White to off-white solid powder |
| LogP | 1.7 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 33 |
| Complexity | 662 |
| Defined Atom Stereocenter Count | 2 |
| 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 |
| InChi Key | XKQLNDPUQSZBJW-QGHHPUGFSA-N |
| 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 |
| 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 |
| 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) |
Biological Activity
| Targets | IC50: 5 nM (MALT1)[1] Kd: 13 nM (MALT1(329-728)-W580S), 42 nM (MALT1(329-728))[1] |
| 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]. |
| 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. |
| References |
[1]. An allosteric MALT1 inhibitor is a molecular corrector rescuing function in an immunodeficient patient. Nat Chem Biol. 2019 Mar;15(3):304-313. |
Solubility Data
| Solubility (In Vitro) | DMSO: 200 mg/mL (406.24 mM) |
| 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. 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. 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. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |