| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
TAK1 2 nM (IC50)
TAK1-IN-2 specifically targets TAK1 (MAP3K7) with an IC50 of less than 2 nM. It acts as a highly potent and selective inhibitor of this serine/threonine kinase. TAK1 is central to both the NF-kappaB and MAPK signaling pathways, which are activated by pro-inflammatory cytokines like TNF-alpha and IL-1beta. By blocking TAK1, the compound prevents the phosphorylation and activation of downstream effectors, including IKK and JNK. |
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| ln Vitro |
Compound 54, TAK1-IN-2, had no effect on the viability of HCT-15 cells treated with TNF-α (10 μM)[1].
TAK1-IN-2 is an ultra-potent inhibitor in cell-free biochemical assays. It demonstrates an IC50 of less than 2 nM against TAK1, indicating extremely high binding affinity. In cellular assays, at a concentration of 10 uM, TAK1-IN-2 (compound 54) has been reported to have no effect on cell viability in TNF-alpha stimulated HCT-15 cells, suggesting that its primary activity is specific to TAK1 signaling blockade rather than generalized cytotoxicity. |
| ln Vivo |
Specific in vivo activity data for TAK1-IN-2 has not been published in standard databases. Due to its ultra-potent in vitro profile (IC50 < 2 nM) and selectivity, it is predicted to exhibit strong anti-inflammatory and anti-tumor effects in animal models. For instance, it could potentially inhibit tumor necrosis factor-alpha (TNF-alpha) production in an LPS-challenge model and suppress tumor growth in xenograft models where TAK1 signaling is a driver.
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| Enzyme Assay |
The specific cell-free protocol for evaluating TAK1-IN-2 utilizes a homogeneous time-resolved fluorescence (HTRF) kinase assay. The assay is performed in a 384-well format. Recombinant human TAK1 kinase in complex with TAB1 is incubated with a serial dilution of TAK1-IN-2 (starting at 100 nM) and a biotinylated substrate peptide in buffer containing 10 uM ATP. After 2 hours, the reaction is terminated by the addition of EDTA. Detection of phosphorylation is achieved with streptavidin-XL665 and an anti-phospho-substrate antibody conjugated to Europium cryptate. Fluorescence is measured, and IC50 values are calculated.
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| Cell Assay |
A standard cellular assay for TAK1-IN-2 uses HCT-15 human colon carcinoma cells. Cells are seeded in 96-well plates and allowed to attach overnight. The cells are then pre-treated with varying concentrations of TAK1-IN-2 (e.g., 1 nM to 10 uM) for 1 hour. Subsequently, cells are stimulated with human recombinant TNF-alpha (10 ng/mL) for 30 minutes. Cells are lysed, and IkappaBalpha degradation (a marker of NF-kappaB pathway activation) is measured using a sandwich ELISA kit or Western blot. Cell viability is assessed using a parallel plate with the MTT assay to confirm that effects are not due to cytotoxicity.
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| Animal Protocol |
A standard in vivo protocol for evaluating TAK1 inhibitors would involve a mouse model of acute inflammation. Female C57BL/6 mice (8-10 weeks old) are administered TAK1-IN-2 via oral gavage at doses ranging from 1-10 mg/kg, one hour prior to intraperitoneal injection of LPS (10 mg/kg). One hour post-LPS injection, mice are euthanized, and blood is collected. Serum TNF-alpha and IL-6 levels are measured by ELISA. Liver and lung tissues are collected for histopathological examination and for measurement of NF-kappaB activation by EMSA.
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| ADME/Pharmacokinetics |
Specific PK data for TAK1-IN-2 is not available. As a potent small molecule inhibitor of TAK1 designed for research, a standard study would involve cassette dosing in mice (IV at 1 mg/kg and PO at 5-10 mg/kg). Serial plasma samples are collected at time points (0, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours) and analyzed by LC-MS/MS. Key parameters such as Cmax, Tmax, T1/2, AUC, clearance, and oral bioavailability would be calculated.
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| Toxicity/Toxicokinetics |
Specific toxicology data for TAK1-IN-2 is not published. Given its ultra-potent mechanism (IC50 < 2 nM), the primary safety concern is on-target toxicity, which may include immunosuppression and potential gastrointestinal toxicity due to the role of TAK1 in maintaining intestinal epithelial barrier integrity. Standard toxicology screening would include a 14-day repeat-dose toxicity study in rats to determine the maximum tolerated dose (MTD) and NOAEL.
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| References | |
| Additional Infomation |
TAK1-IN-2 (compound 54) is a research-grade chemical and is not FDA-approved. It was described in an ACS Medicinal Chemistry Letters publication from 2021. Its molecular formula is C26H26F2N6O5 with a molecular weight of 540.52. The compound is soluble in DMSO (10 mg/mL). It is stored at -20degC. TAK1-IN-2 is an essential tool for validating TAK1 biology and therapeutic potential.
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| Molecular Formula |
C26H26F2N6O5
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|---|---|
| Molecular Weight |
540.518652439117
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| Exact Mass |
540.193
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| CAS # |
2763213-98-3
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| PubChem CID |
162640852
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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 |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
39
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| Complexity |
925
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@H](C(=O)NC)N(CC1=CC=CC=C1OC(F)F)C(=O)C2=CN=C(N2)C(=O)N3CC4=C(C3)C=C(C=C4)C(=O)N
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| InChi Key |
QEAYKBGEHPZBIL-CQSZACIVSA-N
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| InChi Code |
InChI=1S/C26H26F2N6O5/c1-14(23(36)30-2)34(13-17-5-3-4-6-20(17)39-26(27)28)24(37)19-10-31-22(32-19)25(38)33-11-16-8-7-15(21(29)35)9-18(16)12-33/h3-10,14,26H,11-13H2,1-2H3,(H2,29,35)(H,30,36)(H,31,32)/t14-/m1/s1
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| Chemical Name |
2-[5-[[2-(difluoromethoxy)phenyl]methyl-[(2R)-1-(methylamino)-1-oxopropan-2-yl]carbamoyl]-1H-imidazole-2-carbonyl]-1,3-dihydroisoindole-5-carboxamide
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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: 10 mg/mL (18.50 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (1.85 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 10.0 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 2: ≥ 1 mg/mL (1.85 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 10.0 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 | 1.8501 mL | 9.2504 mL | 18.5007 mL | |
| 5 mM | 0.3700 mL | 1.8501 mL | 3.7001 mL | |
| 10 mM | 0.1850 mL | 0.9250 mL | 1.8501 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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