| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Targets |
PDK1 (IC50 = 49 nM); PDK2 (IC50= 101 nM); PDK3 (IC50= 313 nM)
The primary target of JX-06 is pyruvate dehydrogenase kinase (PDK), a family of enzymes (PDK1, PDK2, PDK3, PDK4) that regulate the pyruvate dehydrogenase complex (PDC). PDK phosphorylates and inactivates the E1 subunit of PDC, thereby inhibiting the conversion of pyruvate to acetyl-CoA and shifting cellular metabolism from oxidative phosphorylation to glycolysis. JX-06 is a potent and selective inhibitor of PDK1, PDK2, and PDK3 with IC₅₀ values of 49 nM, 101 nM, and 313 nM, respectively. It is a covalent inhibitor that binds to Cys240 in the ATP-binding pocket of PDK1. |
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| ln Vitro |
JX06 barely shows inhibitory activity against PDK4 at a concentration of 10 μM[1].
JX06 (1-10 μM; 48 hours) induces cell apoptosis in cancer cells with high ECAR/OCR[1].JX06(0-0.6 μM; 72 hours) inhibits the growth of A549 cells in a dose-dependent manner[1]. JX06(0.1-10 μM; 6-24 hours) inhibits PDHA1 phosphorylation in A549 cells in a time- and dose-dependent manner.[1] JX06 (1–10 μM) increases intracellular ATP levels and glucose uptake while decreasing aerobic glycolysis as measured by lactate production in A549 cells[1]. JX06 (1-10 μM; 24 hours) induces ROS generation in cancer cells with high extracellular acidification rate (ECAR)/ oxygen consumption rate (OCR) [1].
In vitro, JX-06 inhibits PDK1, PDK2, and PDK3 with IC₅₀ values of 49 nM, 101 nM, and 313 nM, respectively. It is the first covalent inhibitor of the PDK1 isoform. The compound inhibits PDK1 activity via covalently binding to Cys240 in the ATP-binding pocket. By inhibiting PDK, JX-06 activates PDC and promotes glucose oxidation, shifting cellular metabolism from glycolysis to oxidative phosphorylation. This metabolic modulation has therapeutic potential in cancer treatment. |
| ln Vivo |
JX06 (40-80 mg/kg; i.p. for 21 days) inhibits tumor growth in vivo[1].
In vivo, JX-06 modulates cellular metabolism and represents a targeted therapeutic approach in cancer treatment. By inhibiting PDK and activating PDC, the compound shifts cellular metabolism from glycolysis to oxidative phosphorylation, which may be beneficial in cancer therapy. However, specific in vivo efficacy data from animal models is not detailed in the provided sources. The compound's covalent binding mechanism provides sustained target engagement. |
| Enzyme Assay |
For PDK inhibitors, standard cell-free assays involve measuring the kinase activity of recombinant PDK isoforms using a peptide substrate derived from the E1α subunit of PDC. The compound is incubated with the enzyme, ATP, and substrate, and phosphorylation is detected by radioactive (³³P-ATP) or fluorescent methods to determine IC₅₀ values. Covalent binding to Cys240 can be confirmed by mass spectrometry or mutagenesis studies.
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| Cell Assay |
For PDK inhibitors, standard cellular assays involve treatment of cancer cell lines with the test compound for 24-72 hours. PDK activity is assessed by measuring the phosphorylation status of the E1α subunit of PDC by western blot. Cellular metabolism is assessed by measuring oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Cell viability (MTT or CellTiter-Glo) and apoptosis are assessed.
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| Animal Protocol |
A549 subcutaneous xenograft mice[1]
40, 80 mg/kg I.p. injections for 21 days For in vivo evaluation of PDK inhibitors, standard animal models include tumor xenograft models using cancer cell lines sensitive to metabolic modulation. The compound is typically administered orally or intraperitoneally for 2-4 weeks. Tumor growth, PDK activity, metabolic markers, and survival are assessed. |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for JX-06 is not extensively provided in the available sources. The compound has a molecular weight of 335.16 and formula C₁₀H₁₆N₂O₂S₄. It is also known as Bis(morpholinothiocarbonyl) disulfide. As a small molecule with moderate lipophilicity, it would be expected to have reasonable cell permeability. Comprehensive PK studies would be required for therapeutic development.
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| Toxicity/Toxicokinetics |
Detailed toxicology data for JX-06 is not provided in the available sources. As a research compound targeting PDK, standard preclinical toxicology would be required for therapeutic development. The compound's covalent binding mechanism may raise concerns about off-target reactivity, though its selectivity for PDK suggests a manageable safety profile. The compound is for research use only and not for therapeutic applications.
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| References | |
| Additional Infomation |
JX-06 is a potent, selective, and covalent pyruvate dehydrogenase kinase (PDK) 1/2/3 inhibitor. It inhibits PDK1, PDK2, and PDK3 with IC₅₀ values of 49 nM, 101 nM, and 313 nM, respectively. It is the first covalent inhibitor of PDK1 and has the molecular formula C₁₀H₁₆N₂O₂S₄. No regulatory approval has been identified.
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| Molecular Formula |
C10H16N2O2S4
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|---|---|
| Molecular Weight |
324.49
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| Exact Mass |
324.009
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| Elemental Analysis |
C, 37.02; H, 4.97; N, 8.63; O, 9.86; S, 39.52
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| CAS # |
729-46-4
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| Related CAS # |
729-46-4
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| PubChem CID |
12892
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| Appearance |
White to off-white solid powder
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| Density |
1.463g/cm3
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| Boiling Point |
466.3ºC at 760 mmHg
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| Flash Point |
235.8ºC
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| Index of Refraction |
1.69
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| LogP |
1.477
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
18
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| Complexity |
274
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1COCCN1C(=S)SSC(=S)N2CCOCC2
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| InChi Key |
KKVYOWPPMNSLCP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H16N2O2S4/c15-9(11-1-5-13-6-2-11)17-18-10(16)12-3-7-14-8-4-12/h1-8H2
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| Chemical Name |
morpholine-4-carbothioylsulfanyl morpholine-4-carbodithioate
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| Synonyms |
JX06 JX 06 JX-06
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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: 50~65 mg/mL (154.1~200.3 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.70 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 25.0 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: 2.5 mg/mL (7.70 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (7.70 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 | 3.0818 mL | 15.4088 mL | 30.8176 mL | |
| 5 mM | 0.6164 mL | 3.0818 mL | 6.1635 mL | |
| 10 mM | 0.3082 mL | 1.5409 mL | 3.0818 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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