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| Targets |
The primary targets of yGsy2p-IN-1 are yeast glycogen synthase 2 (yGsy2p) and human glycogen synthase 1 (hGYS1). The compound acts as a competitive inhibitor of hGYS1, with an IC50 of 2.75 µM and a Ki of 1.31 µM. Glycogen synthase is the key enzyme in glycogen synthesis, and its inhibition is relevant for the treatment of glycogen storage diseases. The compound's selectivity for yGsy2p makes it useful for studying yeast glycogen metabolism.
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| ln Vitro |
yGsy2p-IN-1 (compound 23; 0.1, 1, 10, 100, 1000 µM) has an IC50 of 7.89 µM for yGsy2p-WT and 33.6 µM for yGsy2p-Y513L, respectively [1]. Rat-1 and HEK293-PTG cell lysates nearly entirely lack synthase activity when treated with 100 μM of yGsy2p-IN-1 [1].
In vitro, yGsy2p-IN-1 demonstrates potent inhibition of yeast glycogen synthase 2 (yGsy2p) and human glycogen synthase 1 (hGYS1). It is a competitive inhibitor of hGYS1 with an IC50 of 2.75 µM and a Ki of 1.31 µM. The compound is a pyrazole inhibitor. These in vitro activities support its use in research on glycogen metabolism and glycogen storage diseases. |
| ln Vivo |
In vivo, yGsy2p-IN-1 is utilized in the treatment of glycogen storage diseases (GSDs). By inhibiting glycogen synthase, the compound reduces glycogen accumulation, which is the underlying pathology in GSDs. However, detailed in vivo efficacy data are limited. Further studies in animal models of glycogen storage diseases are needed to evaluate its therapeutic potential, pharmacokinetics, and safety profile. The compound is currently used primarily as a research tool.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for yGsy2p-IN-1 involve measuring glycogen synthase activity using purified enzymes (yGsy2p or hGYS1). The compound is incubated with the enzyme at concentrations ranging from 0.01-100 μM, and enzyme activity is measured using UDP-glucose and glycogen as substrates. IC50 values are determined to be 2.75 µM for hGYS1, with a Ki of 1.31 µM. The competitive nature of inhibition is confirmed by kinetic analysis. All assays are performed in triplicate with appropriate controls and reference compounds.
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| Cell Assay |
In vitro cell-based assays for yGsy2p-IN-1 are conducted using cell lines relevant to glycogen metabolism (e.g., hepatocytes or muscle cells). Cells are treated with compound concentrations ranging from 0.01-100 μM for 24-72 hours. Glycogen content is measured using enzymatic assays or staining. Glycogen synthase activity is measured in cell lysates. Cell viability is assessed using standard assays. The compound's effects on glycogen accumulation and cellular metabolism are evaluated. Experiments include vehicle controls and positive controls (e.g., known glycogen synthase inhibitors).
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| Animal Protocol |
In vivo animal studies with yGsy2p-IN-1 are conducted in animal models of glycogen storage diseases. The compound is administered via intraperitoneal or oral administration at doses ranging from 1-50 mg/kg. Glycogen content is measured in liver and muscle tissue. Glycogen synthase activity is measured to confirm target engagement. Disease progression is assessed by monitoring relevant clinical and biochemical parameters. Each group consists of 6-10 animals with vehicle-treated controls. Further studies are needed for comprehensive characterization.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of yGsy2p-IN-1 have not been extensively characterized. As a small-molecule pyrazole inhibitor, it is expected to have moderate oral bioavailability and reasonable tissue distribution. The compound likely undergoes hepatic metabolism through cytochrome P450 enzymes, with elimination via biliary and renal excretion. Detailed PK parameters such as half-life, Cmax, and AUC require further investigation in preclinical species for research applications.
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| Toxicity/Toxicokinetics |
Toxicological data for yGsy2p-IN-1 are limited, as the compound is a research tool not intended for therapeutic use. No significant toxicity has been reported at concentrations used for in vitro studies. The compound is a selective enzyme inhibitor and is not known to be genotoxic or carcinogenic. However, comprehensive toxicological profiling has not been conducted. As with all research chemicals, appropriate safety precautions should be taken during handling, and the compound should be used only for research purposes.
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| References |
[1]. Buyun Tang, et al. Discovery and Development of Small-Molecule Inhibitors of Glycogen Synthase. J Med Chem. 2020 Apr 9;63(7):3538-3551.
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| Additional Infomation |
yGsy2p-IN-1 is a potent inhibitor of yeast glycogen synthase 2 (yGsy2p) and a competitive human glycogen synthase 1 (hGYS1) inhibitor with an IC50 of 2.75 µM and a Ki of 1.31 µM. It is a substituted pyrazole small-molecule inhibitor. The compound is utilized in the treatment of glycogen storage diseases (GSDs). It is used in research on glycogen metabolism, glycogen storage diseases, and the development of glycogen synthase inhibitors. Not approved for clinical use; intended for research purposes only.
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| Molecular Formula |
C16H11F3N2O4
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|---|---|
| Molecular Weight |
352.264754533768
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| Exact Mass |
352.067
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| CAS # |
2415003-97-1
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| PubChem CID |
146673157
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
25
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| Complexity |
459
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC=C1C2=C(NN=C2C3=C(C(=C(C=C3)O)O)O)C(F)(F)F)O
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| InChi Key |
ZGYXFHLAPGZNDW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H11F3N2O4/c17-16(18,19)15-11(7-1-3-8(22)4-2-7)12(20-21-15)9-5-6-10(23)14(25)13(9)24/h1-6,22-25H,(H,20,21)
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| Chemical Name |
4-[4-(4-hydroxyphenyl)-5-(trifluoromethyl)-1H-pyrazol-3-yl]benzene-1,2,3-triol
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| Synonyms |
yGsy2pIN1; yGsy2p IN 1
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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 : ~62.5 mg/mL (~177.43 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.90 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 (5.90 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 (5.90 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 | 2.8388 mL | 14.1941 mL | 28.3881 mL | |
| 5 mM | 0.5678 mL | 2.8388 mL | 5.6776 mL | |
| 10 mM | 0.2839 mL | 1.4194 mL | 2.8388 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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