| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg | |||
| Other Sizes |
| Targets |
AMPK α2β2γ1 0.13 μM (EC50) AMPK α1β1γ1 0.42 μM (EC50) AMPK α2β1γ1 0.95 μM (EC50)
ZLN024 hydrochloride targets AMP-activated protein kinase (AMPK). It allosterically stimulates active AMPK heterotrimers, increasing the activity of α1β1γ1 by 1.5-fold and α2β1γ1 by 1.7-fold. ZLN024 requires Thr-172 to be pre-phosphorylated by upstream kinases and prevents PP2Cα from dephosphorylating AMPK Thr-172. |
|---|---|
| ln Vitro |
ZLN024 exhibits allosteric stimulation of both the inactive α1 subunit truncations, α1 (1-394) and α1 (1-335), as well as active AMPK heterotrimers, but not α1 (1-312). ZLN024 triggers AMPK activation by requiring Thr-172 to be pre-phosphorylated by a minimum of one upstream kinase. This prevents PP2Cα from dephosphorylating AMPK Thr-172. Without raising the ADP/ATP ratio, ZLN024 stimulates fatty acid oxidation and glucose uptake in L6 myotubes by activating AMPK. ZLN024, a new AMPK activator, is discovered through random screening against the AMPK α1β1γ1 heterotrimer using the well-established scintillation proximity assay (SPA) assay. In a concentration-dependent manner, ZLN024 directly activates recombinant AMPK α1β1η1 and its homologue α2β1η1. ZLN024 exhibits a 1.5-fold increase in α1β1η1 activity, with an EC50 of 0.42 µM, and a 1.7-fold rise in α2β1η1 activity, with an EC50 of 0.95 µM. ZLN024 also has an EC50 of 1.1 µM; 0.13 µM, directly activating recombinant AMPK α1β2γ1 by 1.7-fold[1].
ZLN024 exhibits allosteric stimulation of both the inactive α1 subunit truncations, α1 (1-394) and α1 (1-335), as well as active AMPK heterotrimers, but not α1 (1-312). It directly activates recombinant AMPK α1β1γ1 and its homologue α2β1γ1 in a concentration-dependent manner. ZLN024 has no effect on mitochondrial function or the ADP/ATP ratio. |
| ln Vivo |
For five weeks, ZLN024 at a dose of 15 mg/kg/day is given to C57BKS db/db mice by daily gavage; 250 mg/kg/day of Metformin (Met) is used as a positive control. When compared to the vehicle group, there is no discernible difference in the amount of food consumed or body weight over the treatment period. ZLN024 enhances glucose tolerance following a 4-week course of therapy. ZLN024 lowers blood glucose levels by 15% when fasting. Triacylglycerol, total cholesterol, and liver tissue weight are all reduced[1].
ZLN024 (15 mg/kg/day; daily gavage for five weeks) is given to C57BKS db/db mice. It enhances glucose tolerance following a 4-week course of therapy. ZLN024 lowers fasting blood glucose levels by 15%. Triacylglycerol, total cholesterol, and liver tissue weight are all reduced. |
| Enzyme Assay |
In vitro enzyme assays measure the direct activation of recombinant AMPK heterotrimers using scintillation proximity assay (SPA). EC50 values are determined for various AMPK isoforms including α1β1γ1, α2β1γ1, α1β2γ1, and α2β2γ1.
|
| Cell Assay |
Cell-based assays use L6 myotubes to measure AMPK activation, glucose uptake, and fatty acid oxidation. ZLN024 stimulates these metabolic effects through AMPK activation without affecting the ADP/ATP ratio. The compound's activity is confirmed through Western blot analysis of AMPK phosphorylation.
|
| Animal Protocol |
In vivo efficacy is evaluated in C57BKS db/db mice, a model of type 2 diabetes. ZLN024 is administered at 15 mg/kg/day by daily gavage for five weeks. Metformin (250 mg/kg/day) is used as a positive control. Glucose tolerance, fasting blood glucose, and lipid parameters are measured.
|
| ADME/Pharmacokinetics |
ZLN024 hydrochloride is orally bioavailable. It is administered by daily gavage in animal studies. The compound activates AMPK allosterically and requires Thr-172 phosphorylation for activity. It has no effect on mitochondrial function or the ADP/ATP ratio.
|
| Toxicity/Toxicokinetics |
Preclinical toxicity data for ZLN024 hydrochloride are limited. In animal studies, no discernible difference in food consumption or body weight was observed over the treatment period compared to vehicle. Standard laboratory safety precautions should be followed. Further toxicological studies are needed for comprehensive safety assessment.
|
| References | |
| Additional Infomation |
ZLN024 hydrochloride is an allosteric AMPK activator that stimulates glucose uptake and fatty acid oxidation. It improves glucose tolerance and reduces lipid parameters in diabetic mouse models. The compound is a valuable research tool for studying AMPK-mediated metabolic regulation and potential therapeutic applications in metabolic disorders such as type 2 diabetes and obesity.
|
| Molecular Formula |
C13H14BRCLN2OS
|
|---|---|
| Molecular Weight |
361.6851
|
| Exact Mass |
359.969
|
| CAS # |
1883548-91-1
|
| Related CAS # |
ZLN024;723249-01-2
|
| PubChem CID |
91654626
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
19
|
| Complexity |
239
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
BrC1C([H])=C(C([H])([H])[H])C([H])=C([H])C=1OC([H])([H])C([H])([H])SC1=NC([H])=C([H])C([H])=N1.Cl[H]
|
| InChi Key |
MMQCYIMDROWWFE-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C13H13BrN2OS.ClH/c1-10-3-4-12(11(14)9-10)17-7-8-18-13-15-5-2-6-16-13;/h2-6,9H,7-8H2,1H3;1H
|
| Chemical Name |
2-[2-(2-bromo-4-methylphenoxy)ethylsulfanyl]pyrimidine;hydrochloride
|
| 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, avoid exposure to moisture. |
| 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 : ≥ 46 mg/mL (127.18 mM)
H2O : < 0.1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.91 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 (6.91 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 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 (6.91 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 | 2.7648 mL | 13.8240 mL | 27.6480 mL | |
| 5 mM | 0.5530 mL | 2.7648 mL | 5.5296 mL | |
| 10 mM | 0.2765 mL | 1.3824 mL | 2.7648 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
