| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| 1g | |||
| Other Sizes |
| Targets |
The primary target of KHK-IN-8 is ketohexokinase (KHK), also known as hexulokinase. KHK is the enzyme responsible for the phosphorylation of fructose to fructose-1-phosphate (F1P), the first step in fructose metabolism. KHK-IN-8 is a selective and cell membrane-permeable inhibitor of KHK with an IC50 of 12 nM. It is a reversible and ATP-competitive inhibitor that interacts with Asp-27B in the ATP-binding region of KHK. By inhibiting KHK, the compound reduces F1P production and may have therapeutic potential for metabolic disorders such as diabetes and obesity.
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| ln Vitro |
In human liver microsomes (1A2, 2C19, 2D6, 2C9, and 3A4), KHK-IN-1 does not substantially inhibit cytochrome P450. It is stable in rat and human liver microsomal preparations (88% and 72% residual at 10 min)[1]. With an IC50 value of 400 nM, KHK-IN-1 (0-10 µM; incubate for 30 minutes, then add 15 mM fructose and incubate for an additional 3 hours) suppresses the synthesis of F1P in HepG2 cell lysates [1].
KHK-IN-8 inhibits KHK with an IC50 of 12 nM and F=34%. It inhibits F1P production in HepG2 cell lysates with an IC50 of 400 nM. The compound shows potent cellular KHK inhibition with an IC50 of <500 nM. It is a reversible and ATP-competitive inhibitor that interacts with Asp-27B in the ATP-binding region of KHK. The compound's selectivity for KHK makes it a valuable tool for studying fructose metabolism and its role in metabolic diseases. |
| ln Vivo |
In rats, the oral bioavailability of KHK-IN-1 (10 mg/kg; oral; single dosage) is 34% [1].
No specific in vivo activity data is publicly available for KHK-IN-8. As a KHK inhibitor, it would be expected to reduce fructose metabolism and F1P production in vivo. The compound can be used for studying diabetes and obesity, suggesting potential efficacy in animal models of these metabolic disorders. By inhibiting KHK, the compound may reduce hepatic fat accumulation and improve metabolic parameters. However, specific in vivo studies have not been detailed in the available literature. |
| Enzyme Assay |
No specific non-cell assay protocol is available for KHK-IN-8. For KHK inhibitors, standard cell-free assays use recombinant KHK enzyme and measure F1P production from fructose and ATP. The compound is incubated with the enzyme and substrates, and F1P production is measured by coupled enzyme assays, HPLC, or mass spectrometry. These assays provide quantitative data on the compound's potency (IC50) and mechanism of inhibition (ATP-competitive).
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| Cell Assay |
Cell viability assay [1]
Cell Types: HepG2 Cell Tested Concentrations: 0-10 µM Incubation Duration: Incubate for 30 minutes, then add 15 mM fructose, and incubate for another 3 hrs (hours). Experimental Results: F1P production in HepG2 cell lysate was inhibited (IC50= 400 nm ). No specific cell-based assay protocol is available for KHK-IN-8. For KHK inhibitors, standard cellular assays use HepG2 cells or other hepatocyte cell lines. Cells are treated with KHK-IN-8, and F1P production is measured in cell lysates. The compound's inhibition of cellular KHK activity is assessed to determine cellular potency. Cell viability assays can be performed to assess cytotoxicity. The compound's cell membrane permeability is important for its activity in cellular assays. |
| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat (approximately 250 g) [1].
Doses: 10 mg/kg Route of Administration: po (oral gavage); single Experimental Results:demonstrated reasonable oral bioavailability in rats (F=34%; oral t1/2=4 h), but had a high volume of distribution ( Vdss=32 L/kg) and high clearance (CL=160 mL/min/kg). No specific animal protocol is available for KHK-IN-8. For studying diabetes and obesity, standard in vivo models include high-fat diet-induced obesity in mice or genetically obese models. KHK-IN-8 is administered (route and dose to be determined) for 2-4 weeks. Metabolic parameters including body weight, glucose tolerance, insulin sensitivity, and hepatic fat content are assessed. F1P levels in liver or other tissues can be measured as a pharmacodynamic marker. |
| ADME/Pharmacokinetics |
No detailed pharmacokinetic data is publicly available for KHK-IN-8. The compound has a molecular weight of 422.55 and formula C21H26N8S. The SMILES notation is N(C=1C2=C(C(NCC3CC3)=NC=N2)N=C(N1)N4CCNCC4)C5=C(SC)C=CC=C5. As a small molecule with moderate lipophilicity and cell membrane permeability, it would be expected to have reasonable oral bioavailability. Comprehensive pharmacokinetic studies would be required for therapeutic development.
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| Toxicity/Toxicokinetics |
No detailed toxicology data is publicly available for KHK-IN-8. As a research compound, standard preclinical toxicology would be required for therapeutic development. The compound's selectivity for KHK may contribute to a manageable safety profile, though potential effects on other kinases or off-target proteins would need to be assessed. The compound is for research use only and not for therapeutic applications.
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| References | |
| Additional Infomation |
KHK-IN-8 is also known as KHK-IN-1 and Ketohexokinase inhibitor 8. It has the molecular formula C21H26N8S and molecular weight 422.55. The SMILES notation is N(C=1C2=C(C(NCC3CC3)=NC=N2)N=C(N1)N4CCNCC4)C5=C(SC)C=CC=C5. It is a selective and cell membrane-permeable inhibitor of KHK with an IC50 of 12 nM. The compound inhibits F1P production in HepG2 cell lysates with an IC50 of 400 nM and shows potent cellular KHK inhibition with an IC50 of <500 nM. No clinical trial status has been identified; it is used for studying diabetes and obesity.
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| Molecular Formula |
C21H26N8S
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| Molecular Weight |
422.55
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| Exact Mass |
422.2
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| CAS # |
1303469-70-6
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| Related CAS # |
KHK-IN-1 hydrochloride;1303470-48-5
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| PubChem CID |
53348216
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
646.4±65.0 °C at 760 mmHg
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| Flash Point |
344.7±34.3 °C
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| Vapour Pressure |
0.0±1.9 mmHg at 25°C
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| Index of Refraction |
1.717
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| LogP |
1.33
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
30
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| Complexity |
543
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1N([H])C1C2=C(C(=NC([H])=N2)N([H])C([H])([H])C2([H])C([H])([H])C2([H])[H])N=C(N=1)N1C([H])([H])C([H])([H])N([H])C([H])([H])C1([H])[H]
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| InChi Key |
HFLMLZKGLUEWBU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H26N8S/c1-30-16-5-3-2-4-15(16)26-20-17-18(19(25-13-24-17)23-12-14-6-7-14)27-21(28-20)29-10-8-22-9-11-29/h2-5,13-14,22H,6-12H2,1H3,(H,23,24,25)(H,26,27,28)
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| Chemical Name |
8-N-(cyclopropylmethyl)-4-N-(2-methylsulfanylphenyl)-2-piperazin-1-ylpyrimido[5,4-d]pyrimidine-4,8-diamine
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| Synonyms |
KHKIN8; KHK IN 8; KHK-IN-8
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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 | 2.3666 mL | 11.8329 mL | 23.6658 mL | |
| 5 mM | 0.4733 mL | 2.3666 mL | 4.7332 mL | |
| 10 mM | 0.2367 mL | 1.1833 mL | 2.3666 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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