| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
TC ASK 10 targets apoptosis signal-regulating kinase 1 (ASK1), a member of the MAP3K family that activates the JNK and p38 MAPK pathways in response to oxidative stress, endoplasmic reticulum stress, and inflammatory cytokines. It inhibits ASK1 with an IC50 of 14 nM. It displays selectivity for ASK1 over other kinases including ASK2 (IC50 = 0.51 μM), MEKK1, TAK1, IKKβ, ERK1, JNK1, p38α, GSK-3β, PKCθ and B-raf (IC50 values are > 10 μM).
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| ln Vitro |
In INS-1 pancreatic β-cells, treatment with TC ASK 10 (Compound 10; 0–10 μM; 1 hour; INS-1 cells) at 0.3 μM suppresses the JNK that is produced by streptozotocin (STZ). Additionally, p38 phosphorylation is suppressed in a dose-dependent manner [1].
In vitro studies have demonstrated that TC ASK 10 potently inhibits ASK1 activity with an IC50 of 14 nM. It shows good selectivity for ASK1 over other kinases, including ASK2 with an IC50 of 0.51 μM. TC ASK 10 (0-10 μM) inhibits streptozotocin (STZ)-induced JNK activation in INS-1 pancreatic β cells from 0.3 μM. The compound's potent and selective inhibition of ASK1 makes it a valuable tool for studying ASK1-mediated signaling in cellular stress responses and disease models. |
| ln Vivo |
Rats were used in the pharmacokinetic profile testing. Oral bioavailability of TC ASK 10 (Compound 10·HCl; rat box at 0.1 mg/kg intravenously and 1 mg/kg orally) is good. For TC ASK 10, 0–8 hours, the Cmax, Tmax, and AUCpo are, respectively, 285.1 ng/mL, 1.67 h, and 275.4 ng.h/mL [1].
In vivo studies have shown that TC ASK 10 is orally active. As an orally bioavailable ASK1 inhibitor, it can be administered to animal models to study the role of ASK1 in various disease conditions including diabetes, cardiovascular diseases, and neurodegenerative disorders. The compound's ability to inhibit ASK1-mediated JNK activation translates to in vivo efficacy. Further detailed in vivo pharmacodynamic and efficacy studies are available from the compound's development and characterization data. |
| Enzyme Assay |
In vitro enzyme/receptor binding (non-cell) assays for TC ASK 10 typically involve kinase inhibition studies using recombinant ASK1 protein. The kinase is incubated with increasing concentrations of TC ASK 10 (0.1 nM - 10 μM), ATP, and a specific substrate in kinase assay buffer at 30°C for 30-60 minutes. Phosphorylation of the substrate is measured using either radioactive ³³P-ATP incorporation followed by filter binding and scintillation counting, or through luminescence-based assays such as ADP-Glo. IC50 values are calculated from dose-response curves by nonlinear regression. Selectivity profiling is performed using a panel of kinases at a fixed compound concentration (e.g., 1 μM).
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: INS-1 Cell Tested Concentrations: 0 μM, 0.3 μM, 1 μM, 3 μM, 10 μM Incubation Duration: 1 hour Experimental Results: Streptozotocin (STZ) found to inhibit streptozotocin (STZ) in INS- Induced JNK 1 pancreatic beta cells at a concentration of 0.3 μM. Phosphorylation of p38 was also inhibited in a dose-dependent manner. For in vitro cell-based assays, INS-1 pancreatic β cells or other relevant cell lines are cultured in appropriate media. Cells are treated with TC ASK 10 at concentrations ranging from 0.01-10 μM for 1-24 hours. ASK1 inhibition is confirmed by measuring the phosphorylation of downstream substrates such as JNK and p38 via Western blot. Cellular stress is induced by treatment with streptozotocin (STZ) or other stress inducers. Cell viability is assessed by MTT or CCK-8 assays. Apoptosis is evaluated by Annexin V/PI staining and caspase-3/7 activity assays. The compound's selectivity can be confirmed by comparing effects on ASK1 versus other MAP3K pathways. |
| Animal Protocol |
In vivo animal studies with TC ASK 10 typically use rodent models of disease where ASK1 plays a pathogenic role. The compound is administered orally at doses determined from pharmacokinetic studies. For diabetes models, STZ-induced diabetic mice are treated with TC ASK 10, and JNK activation in pancreatic tissues is measured. For cardiovascular models, ischemia-reperfusion injury models are used. Blood samples are collected for pharmacokinetic analysis. Tissues are harvested for Western blot analysis of ASK1 downstream signaling, histopathological examination, and assessment of disease-specific biomarkers. Body weight and general health parameters are monitored throughout the study.
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| ADME/Pharmacokinetics |
TC ASK 10 has a molecular weight of 432.35 g/mol and molecular formula C21H21N5O·2HCl. It is soluble in DMSO at 43.23 mg/mL. The compound is orally bioavailable. Storage recommendations: powder at -20°C for 3 years or 4°C for 2 years. Pharmacokinetic parameters including oral bioavailability, Cmax, Tmax, AUC, and half-life are determined in preclinical species. The compound's small molecule nature and favorable properties support its use as a chemical probe for in vivo ASK1 target validation.
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| Toxicity/Toxicokinetics |
In preclinical studies, TC ASK 10 has shown a favorable safety profile at pharmacological doses. As a selective kinase inhibitor, it is well-tolerated in animal models with no significant off-target toxicity reported at therapeutic doses. The compound's selectivity for ASK1 over other kinases reduces the risk of off-target effects. Standard toxicology studies including acute and subchronic toxicity assessments would be required for therapeutic development. The compound is intended for research purposes only and is not approved for human use.
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| References | |
| Additional Infomation |
TC ASK 10 is a potent, selective, and orally active ASK1 inhibitor with an IC50 of 14 nM. It displays selectivity for ASK1 over other kinases including ASK2 (IC50 = 0.51 μM), MEKK1, TAK1, IKKβ, ERK1, JNK1, p38α, GSK-3β, PKCθ and B-raf (IC50 values are > 10 μM). The compound is a valuable research tool for studying ASK1's role in cell survival and stress response, with implications for developing therapeutic strategies for diabetes, cardiovascular diseases, and neurodegenerative disorders. TC ASK 10 is not FDA-approved and is intended for research use only.
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| Molecular Formula |
C21H23CL2N5O
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| Molecular Weight |
432.346222162247
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| Exact Mass |
431.127
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| CAS # |
1005775-56-3
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| PubChem CID |
68661090
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| Appearance |
White to pink solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
525
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)(C)C1=CC=C(C=C1)C(=O)NC2=CN3C=C(C=CC3=N2)N4C=CN=C4.Cl.Cl
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| InChi Key |
IKKLFEDUYFZNBO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H21N5O.2ClH/c1-21(2,3)16-6-4-15(5-7-16)20(27)24-18-13-26-12-17(8-9-19(26)23-18)25-11-10-22-14-25;;/h4-14H,1-3H3,(H,24,27);2*1H
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| Chemical Name |
4-tert-butyl-N-(6-imidazol-1-ylimidazo[1,2-a]pyridin-2-yl)benzamide;dihydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 (~231.29 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.78 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 25.0 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: ≥ 2.5 mg/mL (5.78 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 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.78 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 | 2.3129 mL | 11.5647 mL | 23.1294 mL | |
| 5 mM | 0.4626 mL | 2.3129 mL | 4.6259 mL | |
| 10 mM | 0.2313 mL | 1.1565 mL | 2.3129 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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