| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
IC50: 0.07 μM (PKL)[1]
PKL-IN-1 targets pyruvate kinase L (PKL, also known as PKLR), the L-type isoform of pyruvate kinase. PKL is a key regulatory enzyme in the final step of glycolysis, catalyzing the conversion of phosphoenolpyruvate (PEP) to pyruvate with the generation of ATP. PKL is primarily expressed in the liver and kidney, where it plays a critical role in glucose homeostasis. The compound also inhibits PKR (pyruvate kinase R, the same gene product as PKL but expressed in red blood cells), with IC50 = 0.18 microM. |
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| ln Vitro |
In vitro, PKL-IN-1 (Compound 12a) acts as a potent inhibitor of pyruvate kinase L (PKL) with an IC50 of 0.07 microM. It also inhibits the PKR isoform with an IC50 of 0.18 microM, indicating moderate selectivity for PKL over PKR. At a concentration of 10 microM, the compound inhibits 96.6% of PKL activity. No specific cellular activity data (e.g., effects on glycolysis, ATP levels, or lipogenesis in liver cells) are reported in the search results.
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| ln Vivo |
No specific in vivo activity data for PKL-IN-1 are reported in the search results. However, based on its mechanism as a PKL inhibitor, it has potential applications in research models of non-alcoholic fatty liver disease (NAFLD). Inhibition of PKL in the liver may reduce glycolysis and flux through the pyruvate pathway, potentially affecting de novo lipogenesis (the conversion of glucose-derived pyruvate into fatty acids). Specific dosing and efficacy data in animal models are not available from the search results.
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| Enzyme Assay |
The binding of PKL-IN-1 to pyruvate kinase L (PKL) is measured by standard in vitro enzyme activity assays using purified recombinant PKL enzyme. The compound is incubated with the enzyme, the substrate phosphoenolpyruvate (PEP), and ADP in a reaction buffer. The reaction is allowed to proceed for a defined period, and the amount of pyruvate produced is quantified. Pyruvate is typically measured by coupling the reaction to lactate dehydrogenase (LDH), which converts pyruvate to lactate while oxidizing NADH to NAD+. The decrease in NADH absorbance is measured at 340 nm. IC50 values (0.07 microM for PKL) are calculated from dose-response curves (0.001-100 microM).
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| Cell Assay |
No cellular experiments for PKL-IN-1 are described in the search results. For cellular studies of PKL inhibition, human liver-derived cell lines (e.g., HepG2, Huh7, primary human hepatocytes) are seeded in 6- or 96-well plates. Cells are treated with PKL-IN-1 at graded concentrations (0.01-100 microM) for 24-72 hours. PKL activity is measured in cell lysates using the pyruvate kinase activity assay kit (coupled with LDH). Glycolytic flux is assessed by measuring lactate production in the culture medium or cellular ATP levels. For NAFLD models, cells are treated with free fatty acids (e.g., oleate/palmitate) to induce steatosis, and the effect of PKL-IN-1 on lipid accumulation (Oil Red O staining) is assessed.
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| Animal Protocol |
No animal experiments for PKL-IN-1 are described in the search results. For in vivo evaluation in NAFLD models, 6-8-week-old male C57BL/6 mice are fed a high-fat diet (HFD) for 12-16 weeks to induce NAFLD. PKL-IN-1 would be administered orally at doses of 10-50 mg/kg daily for 4-8 weeks. At the study endpoint, blood would be collected for analysis of fasting glucose, insulin, triglycerides, and cholesterol. Livers would be harvested for histological analysis (H&E and Oil Red O staining), quantification of triglyceride content, and PKL activity assay. Glucose and insulin tolerance tests would be performed during the treatment period.
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| ADME/Pharmacokinetics |
PKL-IN-1 (C12H₈O₈S, MW = 312.25, CAS 2398008-23-8) is a solid powder. For storage, the compound should be kept at -20degC sealed, away from moisture and light. For in vitro use, stock solutions in DMSO (10-50 mM) can be stored at -80degC for up to 6 months or at -20degC for 1 month. For in vivo use, it can be formulated in 10% DMSO / 40% PEG300 / 5% Tween-80 / 45% saline or 0.5% methylcellulose/0.1% Tween-80. Purity is typically ≥98% (HPLC). No detailed PK parameters (oral bioavailability, Cmax, Tmax, half-life) are reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data for PKL-IN-1 are reported in the search results. As a research-grade compound, it is not intended for human or veterinary use. Standard laboratory safety precautions for handling chemicals should be followed, including the use of gloves, lab coat, and safety goggles. Pyruvate kinase is a critical enzyme in glycolysis and energy metabolism; systemic inhibition may cause metabolic disturbances. No LD50 or formal toxicology studies are available.
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| References | |
| Additional Infomation |
PKL-IN-1 (Compound 12a) is a potent inhibitor of pyruvate kinase L (PKL). Pyruvate kinase catalyzes the final, rate-limiting step of glycolysis, converting phosphoenolpyruvate (PEP) to pyruvate and generating ATP. The L (liver) isoform of pyruvate kinase is encoded by the PKLR gene and is expressed in the liver, kidney, and red blood cells. PKL plays a key role in gluconeogenesis and lipogenesis in the liver. Inhibition of PKL has been proposed as a therapeutic strategy for non-alcoholic fatty liver disease (NAFLD) by reducing glycolytic flux and de novo lipogenesis. PKL-IN-1 is for research use only and has not entered clinical trials or received regulatory approval.
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| Molecular Formula |
C12H8O8S
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| Molecular Weight |
312.25
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| Appearance |
Solid powder
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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 : 125 mg/mL (400.32 mM; with sonication)
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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 | 3.2026 mL | 16.0128 mL | 32.0256 mL | |
| 5 mM | 0.6405 mL | 3.2026 mL | 6.4051 mL | |
| 10 mM | 0.3203 mL | 1.6013 mL | 3.2026 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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