| Size | Price | Stock | Qty |
|---|---|---|---|
| 500mg |
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| 1g |
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| Other Sizes |
| Targets |
K-811 targets apoptosis signal-regulating kinase 1 (ASK1, also known as MAP3K5), a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family that activates the JNK and p38 MAP kinase pathways in response to oxidative stress, ER stress, and inflammatory signals. ASK1 is a key mediator of apoptosis and inflammation in neurodegenerative and cardiovascular diseases.
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|---|---|
| ln Vitro |
In vitro, K-811 (0.1-10 uM) inhibits ASK1 activity, blocking the phosphorylation of downstream targets such as MKK3/6 and p38. It prevents cell proliferation in cell lines with high ASK1 expression and in HER2-overexpressing GC cells. Apoptosis is induced in cancer cell lines as evidenced by PARP cleavage and caspase-3 activation.
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| Enzyme Assay |
For non-cellular ASK1 inhibition, purified recombinant human ASK1 (full-length or kinase domain) is incubated with a substrate protein (e.g., MBP or myelin basic protein) in kinase reaction buffer containing [gamma-32P]ATP. Varying concentrations of K-811 (0.1-100 uM) are added, and reactions are incubated for 30-60 minutes at 30degC. The phosphorylated substrate is captured on filter papers or by gel electrophoresis, and radioactivity is measured to determine IC50 and Ki values.
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| Cell Assay |
For cell-based assays, ASK1-high cancer cell lines or HER2-overexpressing GC cells are seeded in 96-well plates and treated with K-811 (0.1-10 uM) for 24-72 hours. Cell viability is measured by MTT or CellTiter-Glo. ASK1 activity is assessed by Western blotting for phosphorylated ASK1 (p-ASK1), phosphorylated p38 (p-p38), and phosphorylated JNK (p-JNK).
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| Animal Protocol |
For in vivo evaluation, female BALB/c nu/nu mice are subcutaneously implanted with HER2-overexpressing GC cells (5 × 10⁶ cells). When tumors reach 100-200 mm3, K-811 (5-50 mg/kg) is administered orally or intraperitoneally once daily for 14-28 days. Tumor volume is measured twice weekly. For ALS studies, SOD1-G93A transgenic mice (model of amyotrophic lateral sclerosis) are dosed with K-811 (10-30 mg/kg) daily from pre-symptomatic stage (day 50) onward. Survival is monitored, and motor function is assessed by rotarod and grip strength tests. Spinal cord tissue is harvested for analysis of ASK1-p38 pathway activation.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for K-811 are limited. As a small molecule (MW 510.5, C29H26N4O5), it is expected to have moderate oral bioavailability. The compound is likely to cross the blood-brain barrier (BBB) based on its CNS activity in ALS models. No detailed PK parameters (Cmax, Tmax, AUC, t½) are publicly available.
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| Toxicity/Toxicokinetics |
Formal toxicology studies for K-811 have not been published. In preclinical studies, K-811 appears to be well tolerated at effective doses, with no significant body weight loss or adverse behavioral changes reported. In vitro cytotoxicity assessments in non-cancer cell lines show a favorable safety window.
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| Additional Infomation |
K-811 is a research-grade ASK1 inhibitor, not approved for human therapy. Its value lies in exploring ASK1 as a therapeutic target in ALS, stroke, cardiac ischemia-reperfusion injury, and HER2-positive gastric cancer. The compound is protected by patent US20190256531A1. No clinical trials are registered for K-811.
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| Molecular Formula |
C29H26N4O5
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|---|---|
| Molecular Weight |
510.5
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| Exact Mass |
510.19
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| Elemental Analysis |
C, 68.22; H, 5.13; N, 10.97; O, 15.67
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| CAS # |
1355228-38-4
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| Related CAS # |
1355228-38-4;1355228-39-5;
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| PubChem CID |
56644085
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| Appearance |
Solid powder
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| LogP |
4.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
38
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| Complexity |
873
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)N1C=C(C(=O)C2=CC=CC=C21)C(=O)NC3=CC=C(C=C3)OC4=CN=NC5=CC(=C(C=C54)OC)OC
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| InChi Key |
JVQKIXBAOVAPKB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H26N4O5/c1-17(2)33-16-22(28(34)20-7-5-6-8-24(20)33)29(35)31-18-9-11-19(12-10-18)38-27-15-30-32-23-14-26(37-4)25(36-3)13-21(23)27/h5-17H,1-4H3,(H,31,35)
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| Chemical Name |
N-[4-(6,7-dimethoxycinnolin-4-yl)oxyphenyl]-4-oxo-1-propan-2-ylquinoline-3-carboxamide
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| Synonyms |
K811; K811; K 811
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9589 mL | 9.7943 mL | 19.5886 mL | |
| 5 mM | 0.3918 mL | 1.9589 mL | 3.9177 mL | |
| 10 mM | 0.1959 mL | 0.9794 mL | 1.9589 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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