| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
ASK1 32.8 nM (IC50)
ASK1-IN-2 targets apoptosis signal-regulating kinase 1 (ASK1). The compound inhibits ASK1 kinase activity with an IC50 of 32.8 nM. ASK1 is a key upstream activator of the p38 MAPK and JNK signaling pathways, which are involved in stress responses, inflammation, and apoptosis. By inhibiting ASK1, ASK1-IN-2 blocks the activation of these downstream pathways, thereby reducing inflammation, apoptosis, and other cellular responses. The compound is orally active, making it suitable for in vivo studies and potential therapeutic applications. |
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| ln Vitro |
In AP1-HEK293 cells, ASK1-IN-2 (compound 19) (10 mM; 1 h) reduces luciferase reporter activity with a 95.59% suppression rate[1].
ASK1-IN-2 has demonstrated potent in vitro activity with an IC50 of 32.8 nM against ASK1 in kinase inhibition assays. The compound’s selectivity for ASK1 over other kinases has not been detailed in the available literature, but it is described as a selective inhibitor of ASK1. The compound has potential therapeutic applications for ulcerative colitis, as it modulates inflammatory pathways mediated by ASK1. The half-maximal effective concentration (EC50) for the inhibition of downstream signaling pathways has not been detailed in the available literature. |
| ln Vivo |
In mice, dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) is ameliorated by ASK1-IN-2 (25 mg/kg; po daily for 7 d)[1]. In mouse colon tissues treated with DSS, ASK1-IN-2 (25 mg/kg; po daily for 7 days) inhibits the ASK1-p38/JNK signaling pathways and lowers inflammatory cytokine levels[1]. In rats, ASK1-IN-2 (1 mg/kg; iv) has a moderate half-life (T1/2=1.45 h) and poor clearance (CL=1.38 L/h/kg[1]. Rats treated with ASK1-IN-2 (10 mg/kg; po) exhibit high oral exposure (AUClast=4517 h·ng/mL), 62.2% oral bioavailability, and a tolerable terminal half-life (T1/2=2.31 h)[1].
ASK1-IN-2 has potential therapeutic applications for ulcerative colitis based on its ability to modulate inflammatory pathways mediated by ASK1. No detailed in vivo activity data for ASK1-IN-2 has been published in the available literature. Further studies would be needed to evaluate the efficacy of ASK1-IN-2 in animal models of ulcerative colitis or other inflammatory diseases. The compound’s oral activity makes it suitable for in vivo studies. |
| Enzyme Assay |
The kinase inhibitory activity of ASK1-IN-2 can be assessed using in vitro kinase assays. In a typical assay, recombinant ASK1 kinase is incubated with a peptide substrate, ATP (including radiolabeled ³³P-ATP), and varying concentrations of ASK1-IN-2. The incorporation of phosphate into the substrate is measured, and the half-maximal inhibitory concentration (IC50) is calculated from dose-response curves. The IC50 for ASK1 inhibition is 32.8 nM. The selectivity of ASK1-IN-2 against a panel of other kinases can be assessed using kinase profiling services to determine its off-target effects.
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| Cell Assay |
The cellular activity of ASK1-IN-2 is assessed using cell lines or primary cells that express ASK1. Cells are treated with ASK1-IN-2 at varying concentrations and stimulated with stress signals that activate ASK1, such as oxidative stress (H₂O₂) or pro-inflammatory cytokines (TNF-α). The phosphorylation of ASK1 and its downstream targets, including p38 MAPK and JNK, is assessed by Western blotting using phospho-specific antibodies. The effects of ASK1-IN-2 on apoptosis are assessed by measuring caspase-3/7 activity or by flow cytometry using annexin V/propidium iodide staining. The effects of ASK1-IN-2 on inflammation are assessed by measuring the production of pro-inflammatory cytokines by ELISA.
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| Animal Protocol |
Animal/Disease Models: Male ICR mice (18 -22 g, 6-8 weeks) were given 3% DSS (w/v) orally in drinking water[1]
Doses: 25 mg/kg Route of Administration: Po daily for 7 days Experimental Results: Induced a significant recovery of body weight loss, with an increase of +11.2%. diminished the disease activity index (DAI) score about a 2 unit. Dramatically prevented colon shortening. Attenuated a severe colonic tissue damage and infiltration of inflammatory cells. Animal/Disease Models: Male SD rats [1] Doses: 1 mg/kg for iv; 10 mg/kg for po (pharmacokinetic/PK Analysis) Route of Administration: Iv and po administration Experimental Results: Iv: CL=1.38 L/h/kg; T1/2=1.45 h. Po: AUClast=4517 h• ng/mL; F=62.2%; T1/2=2.31 h. No detailed in vivo animal model data for ASK1-IN-2 has been published in the available literature. The compound has been suggested to have potential therapeutic applications for ulcerative colitis. Future studies may involve the use of mouse models of ulcerative colitis, such as dextran sulfate sodium (DSS)-induced colitis, to assess the efficacy of ASK1-IN-2 in reducing inflammation and tissue damage. The compound’s oral activity makes it suitable for oral administration in these models. |
| ADME/Pharmacokinetics |
No detailed pharmacokinetic data for ASK1-IN-2 has been published in the available literature. The compound is described as orally active, suggesting that it has favorable oral bioavailability. Further studies would be needed to characterize the absorption, distribution, metabolism, and excretion (ADME) properties of ASK1-IN-2, including plasma protein binding, clearance, half-life, and tissue distribution. The compound’s pharmacokinetic profile would be essential for determining appropriate dosing regimens for in vivo efficacy studies.
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| Toxicity/Toxicokinetics |
No detailed toxicity data for ASK1-IN-2 has been published in the available literature. As a research compound, ASK1-IN-2 has not been subjected to comprehensive toxicology studies. The mechanism of action, which involves the inhibition of ASK1 and downstream p38 MAPK and JNK signaling pathways, could have off-target effects in normal tissues. Further studies would be needed to assess the safety profile of ASK1-IN-2.
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| References | |
| Additional Infomation |
ASK1-IN-2 is a potent and orally active inhibitor of apoptosis signal-regulating kinase 1 (ASK1), with an IC50 of 32.8 nM. The compound inhibits ASK1 kinase activity, blocking the activation of downstream p38 MAPK and JNK signaling pathways. ASK1-IN-2 has potential therapeutic applications for ulcerative colitis, as it modulates inflammatory pathways mediated by ASK1. The compound is a valuable tool for studying the role of ASK1 in various diseases and for exploring potential therapeutic strategies.
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| Molecular Formula |
C19H17FN6O
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|---|---|
| Molecular Weight |
364.3763
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| Exact Mass |
364.144
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| CAS # |
2541792-70-3
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| PubChem CID |
155671000
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| Appearance |
White to off-white solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
27
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| Complexity |
534
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C([H])=C([H])C2C([H])=C(C(N([H])C3=C([H])C([H])=C([H])C(C4=NN=C([H])N4C([H])(C([H])([H])[H])C([H])([H])[H])=N3)=O)N([H])C=2C=1[H]
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| InChi Key |
LYUQNMNUBOUCBX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H17FN6O/c1-11(2)26-10-21-25-18(26)14-4-3-5-17(23-14)24-19(27)16-8-12-6-7-13(20)9-15(12)22-16/h3-11,22H,1-2H3,(H,23,24,27)
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| Chemical Name |
6-fluoro-N-[6-(4-propan-2-yl-1,2,4-triazol-3-yl)pyridin-2-yl]-1H-indole-2-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 : 250 mg/mL (686.10 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.71 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 (5.71 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 | 2.7444 mL | 13.7219 mL | 27.4439 mL | |
| 5 mM | 0.5489 mL | 2.7444 mL | 5.4888 mL | |
| 10 mM | 0.2744 mL | 1.3722 mL | 2.7444 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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