| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
GSK 366 targets kynurenine-3-monooxygenase (KMO), a flavin adenine dinucleotide (FAD)-dependent enzyme that catalyzes the hydroxylation of L-kynurenine to 3-hydroxykynurenine in the kynurenine pathway of tryptophan metabolism. KMO is a key regulatory enzyme in this pathway, and its inhibition shifts the metabolic flux away from neurotoxic metabolites such as 3-hydroxykynurenine and quinolinic acid towards the production of neuroprotective kynurenic acid. GSK 366 exhibits potent inhibitory activity against human KMO with an IC50 of 2.3 nM and against Pseudomonas fluorescens KMO (Pf-KMO) with an IC50 of 0.7 nM.
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| ln Vitro |
In vitro, GSK 366 demonstrates potent inhibition of KMO enzymatic activity with IC50 values of 2.3 nM for human KMO and 0.7 nM for Pseudomonas fluorescens KMO. The compound effectively modulates the production of neuroactive metabolites in the kynurenine pathway, reducing the formation of 3-hydroxykynurenine and increasing the levels of kynurenic acid. GSK 366 shows high selectivity for KMO over other enzymes in the tryptophan metabolism pathway. The compound has a purity of ≥99% and is soluble in DMSO at 250 mg/mL with ultrasonic assistance.
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| ln Vivo |
In vivo, GSK 366 has been investigated for its potential to modulate kynurenine pathway metabolism and exert neuroprotective effects in animal models of neuroinflammation and neurodegenerative diseases. By inhibiting KMO, the compound shifts the balance of neuroactive metabolites towards neuroprotective kynurenic acid, which may have therapeutic implications for conditions such as Huntington's disease and other disorders associated with dysregulated kynurenine metabolism. Detailed in vivo efficacy data are limited in publicly available literature, but the compound's potent KMO inhibition and selectivity make it a promising tool for in vivo pharmacological studies.
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| Enzyme Assay |
Receptor binding or enzyme activity assays for GSK 366 are performed using purified recombinant human KMO or Pseudomonas fluorescens KMO enzymes. Enzyme activity is measured by monitoring the conversion of L-kynurenine to 3-hydroxykynurenine, typically using a spectrophotometric or fluorometric assay. GSK 366 is incubated with the enzyme and substrate at varying concentrations in appropriate assay buffer at room temperature or 37degC for a defined period. The reaction is stopped, and product formation is quantified to determine IC50 values from concentration-response curves. Nonspecific activity is determined in control reactions without inhibitor.
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| Cell Assay |
Cellular assays for GSK 366 are conducted using cell lines or primary cells that express KMO, such as macrophages or microglial cells. Cells are cultured in appropriate media and treated with GSK 366 at various concentrations for defined time periods. KMO activity in cell lysates is measured by quantifying the levels of kynurenine pathway metabolites using HPLC or LC-MS/MS. Cell viability and cytotoxicity are assessed using standard assays such as MTT or CellTiter-Glo to determine the compound's selectivity and safety profile. The compound is typically dissolved in DMSO and diluted in cell culture media for treatment.
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| Animal Protocol |
In vivo studies with GSK 366 are conducted in rodent models of neuroinflammation or neurodegenerative diseases. The compound is administered via appropriate routes (e.g., intraperitoneal, oral, or subcutaneous) at defined doses and schedules. Tissue and plasma samples are collected at various time points post-administration for analysis of kynurenine pathway metabolites by LC-MS/MS. Behavioral and functional assessments may be performed to evaluate the compound's neuroprotective effects. The compound's solubility in DMSO (250 mg/mL) allows for formulation in suitable vehicles for in vivo administration.
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| ADME/Pharmacokinetics |
GSK 366 has a molecular weight of 361.78 and a molecular formula of C17H16ClN3O4. The compound is soluble in DMSO at 250 mg/mL with ultrasonic assistance. As a small molecule KMO inhibitor, GSK 366 is expected to have favorable oral bioavailability and blood-brain barrier penetration, although detailed pharmacokinetic parameters are not extensively documented in publicly available literature. The compound is stable as a powder at -20degC for up to 3 years and in solution at -80degC for 6 months.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for GSK 366 are not extensively documented in publicly available sources. The compound is intended for research use only and has not been evaluated in formal toxicology studies for clinical development. In preclinical studies, GSK 366 has been administered without reported significant adverse effects at the doses used for efficacy evaluation. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and adherence to institutional biosafety and chemical hygiene guidelines.
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| References | |
| Additional Infomation |
GSK 366 is a potent and selective inhibitor of kynurenine-3-monooxygenase (KMO) with IC50 values of 2.3 nM for human KMO and 0.7 nM for Pseudomonas fluorescens KMO. By modulating the kynurenine pathway of tryptophan metabolism, GSK 366 effectively regulates the production of neuroactive metabolites linked to inflammation and neurodegeneration. The compound is being studied for its therapeutic potential in neuroinflammatory conditions and Huntington's disease. GSK 366 is for research purposes only and is not approved for clinical use.
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| Molecular Formula |
C17H16CLN3O4
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|---|---|
| Molecular Weight |
361.7796
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| Exact Mass |
361.082
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| CAS # |
1953157-39-5
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| PubChem CID |
121415048
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
25
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| Complexity |
469
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1C([H])=C2C(=C([H])C=1O[C@]([H])(C([H])([H])[H])C1C([H])=C([H])C(C([H])([H])[H])=NN=1)ON=C2C([H])([H])C([H])([H])C(=O)O[H]
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| InChi Key |
YWASLAPMFGBZQP-SNVBAGLBSA-N
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| InChi Code |
InChI=1S/C17H16ClN3O4/c1-9-3-4-13(20-19-9)10(2)24-16-8-15-11(7-12(16)18)14(21-25-15)5-6-17(22)23/h3-4,7-8,10H,5-6H2,1-2H3,(H,22,23)/t10-/m1/s1
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| Chemical Name |
3-[5-chloro-6-[(1R)-1-(6-methylpyridazin-3-yl)ethoxy]-1,2-benzoxazol-3-yl]propanoic acid
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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 (~691.03 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.75 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 (5.75 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.75 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 | 2.7641 mL | 13.8206 mL | 27.6411 mL | |
| 5 mM | 0.5528 mL | 2.7641 mL | 5.5282 mL | |
| 10 mM | 0.2764 mL | 1.3821 mL | 2.7641 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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