| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
PPARα:1.8 μM (EC50) PPARγ:0.08 μM (EC50) PPARδ:1.7 μM (EC50) |
|---|---|
| ln Vitro |
Chiglitazar being studied in comparison to rosiglitazone and pioglitazone for PPARγ and WY14643 for PPARα in terms of dosage response. Chiglitazar has a notable increase in both isoform activation. Chiglitazar exhibits PPARγ activating activity that is stronger than pioglitazone but weaker than rosiglitazone. Chiglitazar is more effective than pioglitazone, rosiglitazone, or WY14643, a selective PPARα agonist, in terms of PPARα activation[1].
In vitro, Chiglitazar was studied in comparison to rosiglitazone and pioglitazone for PPARγ and WY14643 for PPARα in terms of dosage response. It exhibits a notable increase in both isoform activation, with PPARγ activating activity that is stronger than pioglitazone but weaker than rosiglitazone. Chiglitazar is more effective than pioglitazone, rosiglitazone, or WY14643 in terms of PPARα activation. |
| ln Vivo |
Plasma glucose levels in the MSG rats treated with rosiglitazone or Chiglitazar after insulin administration are consistently lower than in the vehicle-treated control group. Animals treated with rosiglitazone and chiglitazar had lower fasting PI levels than the control group. Chiglitazar and rosiglitazone-treated MSG obese rats had considerably higher ISIs than the control group. Chiglitazar additionally improves the HOMA indices. The glucose readings in the 5 and 10 mg/kg Chiglitazar and Rosiglitazone treatment groups are considerably lower than those in the vehicle treatment group for IPGTT at 30 minutes after glucose loading. The treatment groups' integrated glucose response during the IPGTT is substantially lower than that of the control groups[1].
In vivo, plasma glucose levels in MSG obese rats treated with Chiglitazar after insulin administration are consistently lower than in vehicle-treated controls. Chiglitazar and rosiglitazone-treated MSG obese rats had considerably higher insulin sensitivity indices (ISIs) than the control group. Chiglitazar additionally improves HOMA indices. In IPGTT at 30 minutes after glucose loading, the 5 and 10 mg/kg Chiglitazar treatment groups showed considerably lower glucose levels than the vehicle group. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays typically involve PPAR ligand-binding domain (LBD) competition binding assays using radiolabeled ligands (e.g., [³H]rosiglitazone for PPARγ). Test compound is incubated with the PPAR LBD at varying concentrations, and binding affinity is determined by measuring displacement of the radioligand. EC50 values are calculated from dose-response curves. For PPARα, WY14643 is used as a reference agonist. Assays are performed in buffer containing appropriate coactivator peptides and detected via fluorescence polarization or scintillation proximity assay.
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| Cell Assay |
Cellular assays typically use HEK293 or COS-1 cells transfected with PPARα, PPARγ, or PPARδ expression plasmids along with a PPAR-responsive luciferase reporter construct (e.g., PPRE-luc). Cells are treated with Chiglitazar at various concentrations for 18-24 hours, followed by luciferase activity measurement. Rosiglitazone and pioglitazone serve as positive controls for PPARγ, while WY14643 is used for PPARα. EC50 values for transactivation are calculated from dose-response curves.
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| Animal Protocol |
In vivo animal studies typically use MSG (monosodium glutamate)-induced obese rats as a model of insulin resistance and type 2 diabetes. Animals are administered Chiglitazar orally at doses of 5 or 10 mg/kg daily for a specified treatment period. Insulin tolerance tests (ITT) and intraperitoneal glucose tolerance tests (IPGTT) are performed to assess glycemic control. Blood glucose levels are measured at various time points, and HOMA-IR and insulin sensitivity indices are calculated.
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| ADME/Pharmacokinetics |
Chiglitazar is orally bioavailable with favorable pharmacokinetic properties. As a small-molecule PPAR agonist, it is expected to have good oral absorption and moderate protein binding. The compound is metabolized primarily via hepatic cytochrome P450 enzymes. Its half-life supports once-daily dosing in clinical settings. Detailed PK parameters such as Cmax, Tmax, AUC, and bioavailability are typically determined in preclinical species (rats and dogs) following oral and intravenous administration.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies of Chiglitazar would typically include acute toxicity in rodents, repeated-dose toxicity (28-day and chronic) in rats and dogs, and genotoxicity assessment (Ames test, chromosome aberration, and micronucleus assay). As a PPAR agonist, potential concerns include fluid retention, weight gain, and cardiovascular effects, which are class effects of PPARγ agonists. In clinical trials, Chiglitazar has demonstrated a favorable safety profile with no significant hepatotoxicity observed.
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| References | |
| Additional Infomation |
Chiglitazar (Bilessglu®) was first granted approval in China in October 2022 for improving glycemic control in adult patients with type 2 diabetes. It is a pan-PPAR agonist that activates PPARα, γ, and δ, regulating glucose and lipid metabolism. The compound upregulates hepatic expression of PPARα target genes and improves insulin resistance and dyslipidemia. It was developed by Chengdu Chipscreen in China. Clinical trials have evaluated its efficacy and safety in diabetic patients.
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| Molecular Formula |
C36H29FN2O4
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|---|---|
| Molecular Weight |
572.6364
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| Exact Mass |
572.211
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| CAS # |
743438-45-1
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| Related CAS # |
2213406-75-6 (racemate free base);1959588-75-0 (racemate sodium);743438-45-1; 2390374-10-2
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| PubChem CID |
71402018
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| Appearance |
Light yellow to khaki solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
779.8±60.0 °C at 760 mmHg
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| Flash Point |
425.4±32.9 °C
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| Vapour Pressure |
0.0±2.8 mmHg at 25°C
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| Index of Refraction |
1.637
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| LogP |
8.72
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
43
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| Complexity |
895
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1=CC=C2C(=C1)C3=CC=CC=C3N2CCOC4=CC=C(C=C4)C[C@@H](C(=O)O)NC5=CC=CC=C5C(=O)C6=CC=C(C=C6)F
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| InChi Key |
QNLWMPLUWMWDMQ-YTTGMZPUSA-N
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| InChi Code |
InChI=1S/C36H29FN2O4/c37-26-17-15-25(16-18-26)35(40)30-9-1-4-10-31(30)38-32(36(41)42)23-24-13-19-27(20-14-24)43-22-21-39-33-11-5-2-7-28(33)29-8-3-6-12-34(29)39/h1-20,32,38H,21-23H2,(H,41,42)/t32-/m0/s1
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| Chemical Name |
(S)-3-(4-(2-(9H-carbazol-9-yl)ethoxy)phenyl)-2-((2-(4-fluorobenzoyl)phenyl)amino)propanoic acid
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| Synonyms |
CS038; CS 038; chiglitazar; 743438-45-1; Carfloglitazar, (s)-; E6EJV1J6Y0; CS-038
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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 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)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~174.64 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.37 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7463 mL | 8.7315 mL | 17.4630 mL | |
| 5 mM | 0.3493 mL | 1.7463 mL | 3.4926 mL | |
| 10 mM | 0.1746 mL | 0.8731 mL | 1.7463 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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