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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Targets |
Saroglitazar targets peroxisome proliferator-activated receptors (PPARs), specifically PPARα (NR1C1) and PPARγ (NR1C3). It acts as a dual PPAR agonist with predominant PPARα activity and moderate PPARγ activity. PPARα activation primarily regulates lipid metabolism, leading to reduced triglyceride and free fatty acid levels. PPARγ activation improves insulin sensitivity and glucose homeostasis. This dual mechanism makes Saroglitazar effective for treating both dyslipidemia and diabetes. The compound's EC50 values are 0.65 pM for PPARα and 3 nM for PPARγ in HepG2 cells.
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| ln Vitro |
In vitro, Saroglitazar magnesium shows predominant PPARα and moderate PPARγ activity with EC50 values of 0.65 pM and 3 nM in HepG2 cells, respectively. These activities confirm its potent and selective PPAR agonist profile. The compound's potent PPARα activation at picomolar concentrations demonstrates its high affinity for this receptor. Its moderate PPARγ activity contributes to its insulin-sensitizing effects while potentially reducing the risk of PPARγ-associated side effects.
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| ln Vivo |
Treatment with Saroglitazar (0.01-3 mg/kg daily, po) for 12 days caused a dose-dependent reduction in blood glucose, free fatty acids (FFA), and triglycerides (TG) in db/db mice. Following oral glucose administration at a dose of 1 mg/kg (59%), the ED50s for these effects of AUC-glucose were found to be 0.05, 0.19, and 0.19 mg/kg, respectively. Saroglitazar's efficacy (TG-lowering capability) was validated in a 90-day repeated dosage comparison research conducted in Wistar rats and marmosets. The study also showed a low risk of PPAR-related side effects in people. Saxoliza shows promise as a novel therapeutic agent for the treatment of diabetes and dyslipidemia based on its efficacy and safety [1].
In vivo, in db/db mice, a 12-day treatment with Saroglitazar (0.01-3 mg/kg per day, orally) causes dose-dependent reductions in serum triglycerides (TG), free fatty acids (FFA), and glucose. The ED50 for these effects is found to be 0.05 mg/kg for TG, 0.19 mg/kg for FFA, and 0.19 mg/kg for glucose. AUC-glucose following oral glucose administration is reduced by 59% at a 1 mg/kg dose. A 90-day repeated dose comparative study in Wistar rats and marmosets confirms the efficacy (TG lowering) potential of Saroglitazar and has indicated a low risk of PPAR-associated side effects in humans. |
| Enzyme Assay |
Non-cell-based receptor binding assays for Saroglitazar use purified PPARα and PPARγ ligand-binding domains (LBDs). The compound is incubated with the receptor LBD and a fluorescently labeled or radiolabeled PPAR ligand at varying concentrations. Binding affinity (EC50 or IC50) is determined by measuring displacement of the labeled ligand or by assessing receptor activation using techniques such as TR-FRET (time-resolved fluorescence resonance energy transfer) or AlphaScreen. Alternatively, PPAR activation can be measured in cell-free transcription assays using nuclear extracts.
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| Cell Assay |
Cellular assays for Saroglitazar utilize HepG2 cells (human hepatocellular carcinoma) to assess PPAR agonism. Cells are transfected with a PPAR response element (PPRE)-driven luciferase reporter construct and treated with the compound at various concentrations. Luciferase activity is measured to quantify PPAR activation. EC50 values for PPARα and PPARγ activation are determined from dose-response curves. PPAR target gene expression (e.g., CPT1A for PPARα, ADIPOQ for PPARγ) may also be measured by qPCR.
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| Animal Protocol |
In vivo animal models for Saroglitazar include db/db mice (a model of type 2 diabetes and obesity). Mice are treated with Saroglitazar orally at doses ranging from 0.01-3 mg/kg per day for 12 days. Serum triglycerides (TG), free fatty acids (FFA), and glucose levels are measured. Oral glucose tolerance tests (OGTT) are performed to assess glucose homeostasis. A 90-day repeated dose study in Wistar rats and marmosets is used to confirm efficacy and assess safety.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Saroglitazar magnesium include a molecular weight of 901.42 g/mol and molecular formula C50H56MgN2O8S2. CAS number is 1639792-20-3. The compound is orally active. Purity is 98.02%. Storage conditions: 4°C, sealed storage, away from moisture; in solvent: -80°C for 2 years; -20°C for 1 year. Detailed PK parameters such as half-life and bioavailability are not extensively reported.
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| Toxicity/Toxicokinetics |
In a 90-day repeated dose comparative study in Wistar rats and marmosets, Saroglitazar has indicated a low risk of PPAR-associated side effects in humans. Detailed toxicological data are not extensively reported, but the compound has been approved for clinical use in India. Given its PPARγ activity, potential side effects would be related to PPARγ agonism, including fluid retention and weight gain. Standard toxicity assessments would evaluate cardiovascular, hepatic, and renal parameters.
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| References | |
| Additional Infomation |
Saroglitazar magnesium is also known as ZYH1, Lipaglyn, and 沙罗格列扎镁盐 in Chinese. It has CAS number 1639792-20-3. It is a novel PPAR agonist with predominant PPARα and moderate PPARγ activity, with EC50 values of 0.65 pM and 3 nM in HepG2 cells, respectively. It was the first glitazar to be granted marketing authorization in India. It is used for dyslipidemia and type 2 diabetes and is being studied for primary biliary cholangitis, NASH, and NAFLD. It is for research use only.
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| Molecular Formula |
C50H56MGN2O8S2
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| Molecular Weight |
901.423252105713
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| Exact Mass |
900.332
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| CAS # |
1639792-20-3
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| Related CAS # |
Saroglitazar;495399-09-2
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| PubChem CID |
121000421
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| Appearance |
Off-white to light yellow solid powder
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
20
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| Heavy Atom Count |
63
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| Complexity |
526
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| Defined Atom Stereocenter Count |
2
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| SMILES |
S(C)C1C=CC(=CC=1)C1=CC=C(C)N1CCOC1C=CC(=CC=1)C[C@@H](C(=O)[O-])OCC.S(C)C1C=CC(=CC=1)C1=CC=C(C)N1CCOC1C=CC(=CC=1)C[C@@H](C(=O)[O-])OCC.[Mg+2]
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| InChi Key |
UJYFZCVPOSZDMK-YPPDDXJESA-L
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| InChi Code |
InChI=1S/2C25H29NO4S.Mg/c2*1-4-29-24(25(27)28)17-19-6-10-21(11-7-19)30-16-15-26-18(2)5-14-23(26)20-8-12-22(31-3)13-9-20;/h2*5-14,24H,4,15-17H2,1-3H3,(H,27,28);/q;;+2/p-2/t2*24-;/m00./s1
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| Chemical Name |
magnesium (S)-2-ethoxy-3-(4-(2-(2-methyl-5-(4-(methylthio)phenyl)-1H-pyrrol-1-yl)ethoxy)phenyl)propanoate
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| Synonyms |
ZYH1; ZYH-1; ZYH 1; trade name: Lipaglyn.
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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, 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)
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| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~138.67 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (3.05 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 27.5 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: 2.75 mg/mL (3.05 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 27.5 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: ≥ 2.75 mg/mL (3.05 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 | 1.1094 mL | 5.5468 mL | 11.0936 mL | |
| 5 mM | 0.2219 mL | 1.1094 mL | 2.2187 mL | |
| 10 mM | 0.1109 mL | 0.5547 mL | 1.1094 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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