TAK1/MAP4K2 inhibitor 1 is a novel, potent dual TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2) inhibitor, with IC50s of 41.1 nM and 18.2 nM, respectively. It possesses good pharmacokinetic properties that will enable their use in pharmacological studies in vivo. A 2.4 Å cocrystal structure of TAK1 in complex with 1 confirms that the activation loop of TAK1 assumes the DFG-out conformation characteristic of type II inhibitors.
Physicochemical Properties
| Molecular Formula | C29H31N6O2F3 |
| Molecular Weight | 552.59064 |
| Exact Mass | 552.246 |
| CAS # | 1315330-11-0 |
| PubChem CID | 71254032 |
| Appearance | White to light yellow solid powder |
| LogP | 6.035 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 40 |
| Complexity | 841 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | RWNAOXLCVXJMGM-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C29H31F3N6O2/c1-4-37-9-11-38(12-10-37)16-21-7-8-22(15-24(21)29(30,31)32)36-27(39)20-6-5-18(2)25(14-20)40-28-23-13-19(3)35-26(23)33-17-34-28/h5-8,13-15,17H,4,9-12,16H2,1-3H3,(H,36,39)(H,33,34,35) |
| Chemical Name | N-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-4-methyl-3-[(6-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]benzamide |
| Synonyms | TAK1/MAP4K2 inhibitor 1; TAK 1/MAP4K2 inhibitor 1; TAK-1/MAP4K2 inhibitor 1 |
| 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
| ln Vivo | The intermediate terminal elimination half-life of TAK1/MAP4K2 inhibitor 1 (1 mg/kg, i.v.) in mice is 2.94 hours [1]. |
| References |
[1]. Discovery of type II inhibitors of TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2). J Med Chem. 2015 Jan 8;58(1):183-96. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~50 mg/mL (~90.48 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (4.98 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 27.5 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: ≥ 2.75 mg/mL (4.98 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 27.5 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8097 mL | 9.0483 mL | 18.0966 mL | |
| 5 mM | 0.3619 mL | 1.8097 mL | 3.6193 mL | |
| 10 mM | 0.1810 mL | 0.9048 mL | 1.8097 mL |