| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
PXL770 targets AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis. It directly activates AMPK with EC50 values of 16.2 nM for the α1β1γ1 isoform, 42.1 nM for α1β1γ2, and 64 nM for α1β1γ3. The compound activates AMPK through both allosteric activation and protection from dephosphorylation, distinguishing it from indirect AMPK activators.
|
|---|---|
| ln Vitro |
In vitro, PXL770 directly activates AMPK with potent EC50 values across multiple isoform combinations. It reduces hepatic de novo lipogenesis (DNL) in vitro. The compound's direct activation of AMPK leads to downstream metabolic effects including improved glucose metabolism and reduced lipid synthesis. Cellular assays demonstrate that PXL770 activates AMPK and its downstream targets, modulating metabolic pathways involved in energy homeostasis and lipid metabolism.
|
| ln Vivo |
In vivo, PXL770 improves glucose metabolism and dyslipidemia in rodent models of metabolic syndrome. In a diet-induced obese (DIO) mouse NASH model, PXL770 ameliorated each of the classical NASH hallmarks, including steatosis, ballooning, inflammation, and fibrogenesis. The compound is orally bioavailable and has demonstrated efficacy in preclinical models of metabolic disease. A Phase 2a clinical trial (STAMP-NAFLD) evaluated its safety and efficacy in NAFLD patients.
|
| Enzyme Assay |
Non-cellular enzyme assays for PXL770 involve measuring AMPK activity using purified enzyme complexes. The compound is incubated with recombinant AMPK heterotrimers (α1β1γ1, α1β1γ2, α1β1γ3) and a peptide substrate. AMPK activity is measured by incorporating 32P-ATP into the substrate, and the EC50 values are determined from dose-response curves. The assay confirms direct activation of AMPK through both allosteric activation and protection from dephosphorylation.
|
| Cell Assay |
In vitro cellular experiments with PXL770 are conducted in hepatocyte cell lines or other metabolically active cells. Cells are treated with the compound at various concentrations, and AMPK phosphorylation (p-AMPK) and downstream target phosphorylation (e.g., ACC) are assessed by Western blotting. Cellular metabolic readouts such as fatty acid oxidation, glucose uptake, and lipid synthesis are measured to evaluate the compound's functional effects on cellular metabolism.
|
| Animal Protocol |
In vivo animal studies for PXL770 are performed in rodent models of metabolic syndrome and NASH. Diet-induced obese (DIO) mice or other metabolic disease models are treated with PXL770 via oral administration. Endpoints include measurements of glucose tolerance, insulin sensitivity, lipid profiles (triglycerides, cholesterol), liver enzymes (ALT, AST), and histopathological assessment of liver tissue for steatosis, inflammation, and fibrosis.
|
| ADME/Pharmacokinetics |
PXL770 has a molecular formula of C23H18ClNO3S and a molecular weight of 423.91. The compound is orally bioavailable. It is typically stored as a solid powder at -20°C for up to 12 months or at 4°C for up to 6 months. In solution, it is stable at -80°C for 6 months or at -20°C for 6 months. It is soluble in DMSO at 10 mM. Purity is typically >98% (HPLC).
|
| Toxicity/Toxicokinetics |
Toxicology data for PXL770 have been generated in preclinical studies and clinical trials. As an AMPK activator, potential effects on energy metabolism in various tissues are monitored. The Phase 2a STAMP-NAFLD trial evaluated the safety and tolerability of PXL770 in patients with NAFLD. Comprehensive toxicology studies would assess safety margins and identify target organ toxicities. Researchers should consult the safety data sheet and handle the compound with appropriate laboratory safety precautions.
|
| References | |
| Additional Infomation |
PXL770 is also known as PXL 770. The IUPAC name is 2-Chloro-4-hydroxy-5-phenyl-3-(5,6,7,8-tetrahydro-1-hydroxy-2-naphthalenyl)thieno[2,3-b]pyridin-6(7H)-one. Key references include a Phase 2a clinical trial publication (Lancet Gastroenterol Hepatol. 2021) and preclinical efficacy studies (Hepatol Commun. 2022). The compound is for research use only and not for human therapeutic applications without regulatory approval.
|
| Molecular Formula |
C23H18CLNO3S
|
|---|---|
| Molecular Weight |
423.91
|
| Exact Mass |
423.069
|
| CAS # |
1523493-53-9
|
| PubChem CID |
72700732
|
| Appearance |
White to off-white solid powder
|
| Density |
1.455±0.06 g/cm3(Predicted)
|
| Boiling Point |
629.5±55.0 °C(Predicted)
|
| LogP |
6
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
29
|
| Complexity |
679
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C12SC(Cl)=C(C3=CC=C4C(=C3O)CCCC4)C=1C(O)=C(C1=CC=CC=C1)C(=O)N2
|
| InChi Key |
KPNBBJGVCJQHBR-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C23H18ClNO3S/c24-21-17(15-11-10-12-6-4-5-9-14(12)19(15)26)18-20(27)16(13-7-2-1-3-8-13)22(28)25-23(18)29-21/h1-3,7-8,10-11,26H,4-6,9H2,(H2,25,27,28)
|
| Chemical Name |
2-chloro-4-hydroxy-3-(1-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-5-phenyl-7H-thieno[2,3-b]pyridin-6-one
|
| HS Tariff Code |
2934.99.9001
|
| 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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO :~120 mg/mL (~283.08 mM; with sonication)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (7.08 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 30.0 mg/mL clear DMSO stock solution and add it to 400 μL PEG300 and mix well. Then add 50 μL Tween-80 to the above system and mix well. Then continue to add 450 μL of physiological saline to make up to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O 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 | 2.3590 mL | 11.7950 mL | 23.5899 mL | |
| 5 mM | 0.4718 mL | 2.3590 mL | 4.7180 mL | |
| 10 mM | 0.2359 mL | 1.1795 mL | 2.3590 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
