| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
Ketohexokinase (KHK), the enzyme that catalyzes the first step of fructose metabolism.
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| ln Vitro |
KHK-IN-1 hydrochloride does not significantly inhibit cytochrome P450 (1A2, 2C19, 2D6, 2C9, and 3A4) and is stable in human and rat liver microsomal preparations (88% and 72% residual at 10 minutes)[1]. HepG2 cell lysate generation of F1P is inhibited by KHK-IN-1 hydrochloride (0-10 µM; incubate for 30 minutes, then add 15 mM fructose and incubate for an additional 3 hours) with an IC50 value of 400 nM [1].
INVIVO-0485 inhibits KHK with IC50 of 12 nM. It inhibits F1P production in HepG2 cell lysates with IC50 of 400 nM. It does not significantly inhibit cytochrome P450 isoforms (1A2, 2C19, 2D6, 2C9, and 3A4) and is stable in human and rat liver microsomes (88% and 72% remaining at 10 min). |
| ln Vivo |
In rats, KHK-IN-1 hydrochloride (10 mg/kg; oral; single dosage) has an oral bioavailability of 34% [1].
INVIVO-0485 inhibits F1P production in HepG2 cells in a dose-dependent manner (0-10 µM; 30 min pre-incubation, then 15 mM fructose for 3 h). It is used to study fructose metabolism and its role in metabolic diseases such as diabetes and obesity. |
| Enzyme Assay |
KHK enzyme activity is measured using a coupled enzyme assay. Recombinant human KHK is incubated with fructose, ATP, and varying concentrations of INVIVO-0485. The production of fructose-1-phosphate (F1P) is quantified by HPLC or coupled enzyme detection. IC50 values are determined from dose-response curves.
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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 ). HepG2 cells are treated with INVIVO-0485 (0-10 µM) for 30 minutes, then stimulated with 15 mM fructose for 3 hours. F1P levels in cell lysates are measured by LC-MS/MS or enzymatic assays to determine inhibition potency. Cell viability is assessed to ensure compound non-toxicity. |
| 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). In male SD rats (approx. 250 g), INVIVO-0485 is administered orally at 10 mg/kg as a single dose. Pharmacokinetic parameters are determined from plasma concentration-time profiles. Oral bioavailability is 34% with oral t1/2 of 4 h. The compound shows high volume of distribution (Vdss = 32 L/kg) and high clearance (CL = 160 mL/min/kg). |
| ADME/Pharmacokinetics |
INVIVO-0485 has molecular weight 459.01 and formula C21H27ClN8S. It is a light yellow to yellow solid powder. In rats, oral bioavailability is 34% with t1/2 of 4 h, Vdss of 32 L/kg, and CL of 160 mL/min/kg. The compound is stable in liver microsomes.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data for INVIVO-0485 are limited. It does not significantly inhibit major CYP450 isoforms, suggesting a low risk of drug-drug interactions. Standard toxicological assessments would be required for clinical development.
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| References | |
| Additional Infomation |
INVIVO-0485 is a research tool for studying fructose metabolism, KHK biology, and metabolic diseases such as diabetes and obesity. Its mechanism involves selective inhibition of KHK, reducing fructose-1-phosphate production and downstream metabolic effects. No clinical trials or approved indications exist.
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| Molecular Formula |
C21H27CLN8S
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|---|---|
| Molecular Weight |
459.013
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| Exact Mass |
458.176
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| CAS # |
1303470-48-5
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| Related CAS # |
KHK-IN-1;1303469-70-6
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| PubChem CID |
92044374
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
31
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| Complexity |
543
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CSC1=CC=CC=C1NC2=NC(=NC3=C2N=CN=C3NCC4CC4)N5CCNCC5.Cl
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| InChi Key |
VKIBPWKARAEIHN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H26N8S.ClH/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);1H
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| Chemical Name |
8-N-(cyclopropylmethyl)-4-N-(2-methylsulfanylphenyl)-2-piperazin-1-ylpyrimido[5,4-d]pyrimidine-4,8-diamine;hydrochloride
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| Synonyms |
INVIVO 0485; INVIVO0485; INVIVO-0485
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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 : ~25 mg/mL (~54.47 mM)
H2O : ~14.29 mg/mL (~31.13 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.53 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 (4.53 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1786 mL | 10.8930 mL | 21.7860 mL | |
| 5 mM | 0.4357 mL | 2.1786 mL | 4.3572 mL | |
| 10 mM | 0.2179 mL | 1.0893 mL | 2.1786 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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