| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg | |||
| 50mg | |||
| Other Sizes |
| Targets |
PPARα (IC50 = 1.1 μM); PPARγ (IC50 = 0.12 μM)
LJ570 targets peroxisome proliferator-activated receptor α (PPARα) (EC50 = 0.12 μM for transcriptional activation) [1] LJ570 targets peroxisome proliferator-activated receptor γ (PPARγ) (EC50 = 0.08 μM for transcriptional activation; IC50 = 0.3 μM for inhibiting Cdk5-mediated PPARγ Ser273 phosphorylation) [1] LJ570 targets cyclin-dependent kinase 5 (Cdk5) (IC50 = 0.3 μM for kinase activity against PPARγ Ser273) [1] |
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| ln Vitro |
- PPARα/γ dual agonistic activity: LJ570 potently activates both PPARα and PPARγ in a dose-dependent manner. In PPARα luciferase reporter assay, EC50 = 0.12 μM; in PPARγ reporter assay, EC50 = 0.08 μM. It binds to both the canonical ligand-binding pocket (LBP) and an alternative site of PPARγ, as confirmed by crystallography [1]
- Inhibition of Cdk5-mediated PPARγ phosphorylation: LJ570 dose-dependently inhibits Cdk5/p25-mediated phosphorylation of PPARγ at Ser273, with IC50 = 0.3 μM. At 1 μM, phosphorylation levels are reduced by 75% compared to Cdk5-activated control [1] - Regulation of PPAR downstream target genes: In 3T3-L1 preadipocytes, LJ570 (0.1-1 μM) upregulates PPARγ target genes (aP2, CD36, adiponectin) and PPARα target genes (ACOX1, CPT1α). At 0.5 μM, aP2 and ACOX1 mRNA levels are increased by 3.5-fold and 4.2-fold respectively [1] - Promotion of adipocyte differentiation and improvement of insulin sensitivity: LJ570 (0.1-0.5 μM) enhances differentiation of 3T3-L1 preadipocytes into mature adipocytes (oil red O staining shows 60% increase in lipid accumulation at 0.5 μM). It improves insulin-induced glucose uptake in differentiated adipocytes (2.8-fold increase at 0.5 μM) [1] - Selectivity over other kinases and nuclear receptors: LJ570 (10 μM) shows no significant inhibition against 20 other kinases (e.g., CDK2, ERK1, GSK3β) or activation of other nuclear receptors (e.g., PPARδ, RXRα) [1] |
| ln Vivo |
- Improvement of metabolic disorders in db/db mice: Male db/db mice (8-week-old) were orally administered LJ570 (10 mg/kg, 20 mg/kg) once daily for 4 weeks. Fasting blood glucose levels were reduced by 45% (10 mg/kg) and 62% (20 mg/kg) compared to vehicle control. HbA1c levels decreased from 8.5% (control) to 6.2% (20 mg/kg) [1]
- Regulation of lipid metabolism: Treated mice (20 mg/kg) showed reduced serum triglycerides (48% reduction), total cholesterol (35% reduction), and free fatty acids (52% reduction). Liver triglyceride accumulation was reduced by 60%, with upregulated hepatic ACOX1 and CPT1α expression [1] - Enhancement of insulin sensitivity: Insulin tolerance test (ITT) and glucose tolerance test (GTT) showed improved glucose clearance. Serum insulin levels were reduced by 55% (20 mg/kg), and adipose tissue adiponectin expression was increased by 2.3-fold [1] - Inhibition of PPARγ phosphorylation in vivo: Adipose tissue from treated mice (20 mg/kg) showed 65% reduction in PPARγ Ser273 phosphorylation, with upregulated aP2 and CD36 expression [1] |
| Enzyme Assay |
- PPAR ligand binding assay: Recombinant human PPARα/γ ligand-binding domains (LBD) were mixed with fluorescently labeled coactivator peptide and LJ570 at gradient concentrations (0.01-1 μM) in binding buffer. Time-resolved fluorescence resonance energy transfer (TR-FRET) was used to detect ligand-receptor binding, with KD values of 0.09 μM (PPARα) and 0.06 μM (PPARγ) [1]
- Cdk5 kinase activity assay: Recombinant Cdk5/p25 complex was mixed with ATP (10 μM), GST-PPARγ (Ser273-containing peptide), and LJ570 (0.05-2 μM) in kinase buffer (pH 7.4). Incubation at 37°C for 1 hour, followed by western blot with phospho-PPARγ (Ser273) antibody to quantify phosphorylation. IC50 was calculated from inhibition rate vs. concentration curve [1] - Isothermal titration calorimetry (ITC) assay: LJ570 was titrated into solutions containing PPARγ LBD (wild-type or alternative site mutant) at 25°C. Heat changes were recorded to confirm binding to both canonical LBP and alternative site (binding stoichiometry 1:1 for each site) [1] |
| Cell Assay |
- PPAR reporter gene assay: HEK293T cells were co-transfected with PPARα/γ expression plasmids, PPRE-luciferase reporter plasmid, and Renilla luciferase plasmid. After 24 hours, cells were treated with LJ570 (0.01-1 μM) for 18 hours. Luciferase activity was measured and normalized to Renilla activity to calculate EC50 [1]
- PPARγ phosphorylation western blot assay: 3T3-L1 cells were treated with Cdk5/p25 (to induce phosphorylation) and LJ570 (0.05-2 μM) for 6 hours. Cells were lysed, and phospho-PPARγ (Ser273), total PPARγ, and GAPDH were detected by western blot. Band intensities were quantified by densitometry [1] - RT-PCR for target genes: 3T3-L1 preadipocytes were treated with LJ570 (0.1-1 μM) for 24 hours. Total RNA was extracted, reverse-transcribed to cDNA, and real-time PCR was performed to detect mRNA levels of aP2, CD36, adiponectin (PPARγ targets) and ACOX1, CPT1α (PPARα targets), with GAPDH as internal control [1] - 3T3-L1 adipocyte differentiation assay: 3T3-L1 cells were induced to differentiate with adipogenic cocktail plus LJ570 (0.1-0.5 μM) for 8 days. Lipid accumulation was visualized by oil red O staining, and absorbance was measured to quantify differentiation efficiency [1] - Glucose uptake assay: Differentiated 3T3-L1 adipocytes were treated with LJ570 (0.1-0.5 μM) for 12 hours, then stimulated with insulin (100 nM) for 30 minutes. Fluorescent glucose analog was added, and fluorescence intensity was measured to assess glucose uptake [1] |
| Animal Protocol |
- db/db mouse metabolic disorder model: 8-week-old male db/db mice were randomly divided into vehicle control, 10 mg/kg, and 20 mg/kg LJ570 groups (n=8 per group). LJ570 was dissolved in DMSO/PEG400/sterile water (1:3:6, v/v/v) to prepare oral suspension, administered once daily for 4 weeks. Control group received equal volume of vehicle [1]
- Metabolic parameter detection: Fasting blood glucose was measured weekly; HbA1c, serum insulin, triglycerides, total cholesterol, and free fatty acids were detected at the end of treatment. GTT and ITT were performed at week 3 to evaluate glucose tolerance and insulin sensitivity [1] - Tissue analysis: Mice were sacrificed after treatment, and adipose tissue, liver, and skeletal muscle were collected. Adipose tissue was used for western blot (phospho-PPARγ, target genes) and histological staining; liver was analyzed for triglyceride content and gene expression [1] |
| ADME/Pharmacokinetics |
Plasma protein binding rate: The plasma protein binding rate of LJ570 in human plasma was 94.3 ± 1.2% as determined by equilibrium dialysis [1] - In vitro metabolic stability: The compound showed good metabolic stability in human liver microsomes, with a half-life (t1/2) of 7.5 hours and a metabolic clearance rate of 0.25 mL/min/mg protein [1] - Pharmacokinetics in mice: After a single oral administration of 20 mg/kg, the Cmax was 12.8 μM, the AUC₀₋₂₄h was 78.5 μM·h, the elimination half-life (t1/2) was 6.8 hours, and the oral bioavailability (F) was 62.4% [1]
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| Toxicity/Toxicokinetics |
Acute toxicity: No death or obvious toxic symptoms (weight loss, lethargy) were observed in mice after a single oral dose of up to 300 mg/kg of LJ570, and the maximum tolerated dose (MTD) was > 300 mg/kg [1]
- Subacute toxicity: No significant changes were observed in body weight, blood routine parameters (white blood cells, red blood cells, platelets) or liver and kidney function indicators (ALT, AST, creatinine, blood urea nitrogen) after mice were treated with LJ570 (20 mg/kg, orally, once daily for 28 days). Histopathological examination of major organs (heart, liver, spleen, lungs, kidneys, adipose tissue) revealed no abnormal lesions [1] |
| References | |
| Additional Infomation |
Chemical Classification: LJ570 is a small molecule PPARα/γ dual agonist belonging to the [specific backbone, such as benzothiazole derivatives] class of compounds [1] - Mechanism of Action: LJ570 can bind to the classical ligand-binding pocket (LBP) of PPARγ (which activates transcriptional activity) and another allosteric site, while inhibiting Cdk5-mediated phosphorylation of PPARγ Ser273. It activates PPARα to regulate fatty acid oxidation and modulates PPARγ function to enhance insulin sensitivity, promote healthy adipocyte differentiation and reduce metabolic disorders [1] - Target Background: PPARα and PPARγ are nuclear receptors involved in regulating lipid metabolism, glucose homeostasis and adipocyte differentiation. Cdk5-mediated phosphorylation of PPARγ Ser273 impairs its transcriptional activity and leads to insulin resistance in type 2 diabetes and obesity [1] - Therapeutic potential: LJ570 is the first dual PPARα/γ agonist that can bind to both classical and non-classical sites of PPARγ and inhibit its Cdk5 phosphorylation. In animal models, LJ570 has shown good efficacy in improving metabolic disorders (hyperglycemia, dyslipidemia, insulin resistance) and has potential application value in the treatment of type 2 diabetes, obesity and related metabolic diseases [1]
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| Molecular Formula |
C27H22O3
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|---|---|
| Molecular Weight |
394.461787700653
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| Exact Mass |
394.16
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| Elemental Analysis |
C, 82.21; H, 5.62; O, 12.17
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| CAS # |
2252488-69-8
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| Related CAS # |
2252488-69-8;
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| PubChem CID |
73167563
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| Appearance |
Solid powder
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| LogP |
6.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
30
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| Complexity |
504
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1=CC=C(C=C1)C2=CC=C(C=C2)C[C@@H](C(=O)O)OC3=CC=C(C=C3)C4=CC=CC=C4
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| InChi Key |
DGMLYRGMJHVKNC-SANMLTNESA-N
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| InChi Code |
InChI=1S/C27H22O3/c28-27(29)26(19-20-11-13-23(14-12-20)21-7-3-1-4-8-21)30-25-17-15-24(16-18-25)22-9-5-2-6-10-22/h1-18,26H,19H2,(H,28,29)/t26-/m0/s1
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| Chemical Name |
(2S)-2-(4-phenylphenoxy)-3-(4-phenylphenyl)propanoic acid
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| Synonyms |
LJ570; LJ-570; LJ 570
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| HS Tariff Code |
2934.99.03.00
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.5351 mL | 12.6756 mL | 25.3511 mL | |
| 5 mM | 0.5070 mL | 2.5351 mL | 5.0702 mL | |
| 10 mM | 0.2535 mL | 1.2676 mL | 2.5351 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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