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Indeglitazar (formerly PPM-204 and PLX-204) is a novel, potent and orally bioavailable pan-agonist for the three PPAR subtypes, alpha (α), delta (δ), and gamma (γ), of the peroxisome proliferator-activated receptor (PPAR). Indeglitazar is a medication being developed to treat Type 2 diabetes (T2DM).
Physicochemical Properties
| Molecular Formula | C19H19NO6S |
| Molecular Weight | 389.42226 |
| Exact Mass | 389.093 |
| Elemental Analysis | C, 58.60; H, 4.92; N, 3.60; O, 24.65; S, 8.23 |
| CAS # | 835619-41-5 |
| Related CAS # | 835619-41-5 |
| PubChem CID | 11395145 |
| Appearance | White to gray solid powder |
| LogP | 3.993 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 27 |
| Complexity | 610 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C(CCC1C2C(=CC=C(C=2)OC)N(S(C2C=CC(OC)=CC=2)(=O)=O)C=1)O |
| InChi Key | YMPALHOKRBVHOJ-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C19H19NO6S/c1-25-14-4-7-16(8-5-14)27(23,24)20-12-13(3-10-19(21)22)17-11-15(26-2)6-9-18(17)20/h4-9,11-12H,3,10H2,1-2H3,(H,21,22) |
| Chemical Name | 3-[5-methoxy-1-(4-methoxyphenyl)sulfonylindol-3-yl]propanoic acid |
| Synonyms | PLX-204; PLX204; PLX 204; PPM-204; PPM204; PPM 204 |
| 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 |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | PPARα; PPARδ; PPARγ |
| ln Vitro | In a preadipocyte differentiation assay, which evaluates the cells' functional insulin sensitization ability, Indeglitazar exhibits an EC50 of 0.32 μM while Rosiglitazone displays an EC50 of 13 nM. Despite this, the two compounds yield comparable maximal responses[1]. |
| ln Vivo | The Zucker rat model of diabetes is used to perform a preliminary evaluation of in vivo activity. Following intravenous treatment with 10 mg/kg Indeglitazar once daily for three weeks, there is a significant reduction in glucose, HbA1C, triglycerides, and total cholesterol. The observed decreases in glucose and HbA1C are accomplished in an adiponectin-independent manner because, remarkably, the level of Adiponectin (on day 21) is essentially unchanged in treated vs. untreated animals (4.8 mcg/mL vs. 4.9 mcg/mL). These variations in Indeglitazar's in vivo effects could be the result of interactions between the compound's three PPAR activities, its SPPARM profile, or a combination of these factors. Using the ob/ob model of diabetes and insulin resistance, the oral activity of Indeglitazar is evaluated. Triglycerides, free fatty acid, insulin, and glucose are all markedly reduced by indglitazar[1]. |
| Enzyme Assay | Before crystallization, equal volumes of a protein or compound sample are mixed with reservoir solution containing 27% polyethylene glycol (PEG) 4000, 0.1 M 2-(bis-(2-hydroxy-ethyl)-amino)-2-hydroxymethyl-propane-1,3-diol (BisTris) buffer at pH 6.5, 0.2 M ammonium acetate, and 5% glycerol. The purified PPAR_ LBD protein is diluted to 12 mg/mL, and 1 mM of Indeglitazar and a 2x molar excess of steroid receptor coactivator-1 (SRC-1) peptide are added prior to crystallization. Before being flash-frozen in liquid nitrogen for data collection, the crystals are soaked in cryo-protective buffer (30% PEG 4000, 0.1 M BisTris buffer at pH 6.5, 0.2 M ammonium acetate, and 5% glycerol)[1]. |
| Animal Protocol |
Rats: To ZDF/GmiCrl-fa/fa rats, indentistazar is given intravenously (10% SolutolHS15, 10% ethanol, 80% saline) once a day. Blood samples are examined 21 days before and after the treatment, which is started at 7-8 weeks of age. Mice: Ob/ob mouse experiment. Nine-week-old B6.V-Lepob mice are given either indagoglitazar (10 mg/kg) or pioglitazone (30 mg/kg) orally for a period of 14 days. Prior to dosing, compounds are suspected in 0.5% methylcellulose and 2% Tween 80. Blood is drawn on the final day to measure adiponectin, insulin, triglycerides, and free fatty acids. |
| References |
[1]. Scaffold-based discovery of Indeglitazar, a PPAR pan-active anti-diabetic agent. Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):262-7. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~100 mg/mL (~256.8 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.42 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 (6.42 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5679 mL | 12.8396 mL | 25.6792 mL | |
| 5 mM | 0.5136 mL | 2.5679 mL | 5.1358 mL | |
| 10 mM | 0.2568 mL | 1.2840 mL | 2.5679 mL |