MA-0204 is a highly potent and selective PPARd modulator (PPARδ EC50 = 0.4 nM; PPARalpha, EC50 == 6,660 nM) that upregulates the expression of FAO genes in human renal proximal tubule cells, resulting in increased mitochondrial fatty acid oxidation. MA-0204 improves renal function, reduces proximal tubular damage, increases mitochondrial gene expression, and attenuates the increases of plasma and urine biomarkers of AKI in normal rats undergoing IR-AKI. DMD patients may benefit from MA-0204 as a treatment.
Physicochemical Properties
| Molecular Formula | C25H27F3N2O4 |
| Molecular Weight | 476.488097429276 |
| Exact Mass | 476.192 |
| Elemental Analysis | C, 63.02; H, 5.71; F, 11.96; N, 5.88; O, 13.43 |
| CAS # | 2095128-17-7 |
| Related CAS # | 2095128-30-4;2095128-17-7 (free acid); |
| PubChem CID | 126752361 |
| Appearance | White to off-white solid powder |
| LogP | 5.8 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 11 |
| Heavy Atom Count | 34 |
| Complexity | 628 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | CC1=CN=C(N1CC2=CC=CC=C2OCCC[C@@H](C)CC(=O)O)C3=CC=C(C=C3)OC(F)(F)F |
| InChi Key | GYNMVDMBFKGCCR-QGZVFWFLSA-N |
| InChi Code | InChI=1S/C25H27F3N2O4/c1-17(14-23(31)32)6-5-13-33-22-8-4-3-7-20(22)16-30-18(2)15-29-24(30)19-9-11-21(12-10-19)34-25(26,27)28/h3-4,7-12,15,17H,5-6,13-14,16H2,1-2H3,(H,31,32)/t17-/m1/s1 |
| Chemical Name | (3R)-3-methyl-6-[2-[[5-methyl-2-[4-(trifluoromethoxy)phenyl]imidazol-1-yl]methyl]phenoxy]hexanoic acid |
| Synonyms | MA 0204MA-0204 MA0204. |
| 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 | PPARδ (EC50 = 0.4 nM); PPARδ (EC50 = 7.9 nM); PPARδ (EC50 = 10 nM) |
| ln Vitro |
MA-0204 exhibits a selectivity of >10,000 times for PPARδ activation relative to PPARα and PPARγ receptors. MA-0204 has good permeability, minimal efflux potential, and high protein binding to mouse plasma.[1]. In mice with DMD, MA-0204 (1.2–12 nM) enhances fatty acid oxidation in the muscle myoblasts[1]. In muscle myoblasts from DMD patients, MA-0204 (0.04–40 nM) activates target gene expression[1]. |
| ln Vivo | In the muscle, PPARδ (30, 100 mg/kg) increases target gene transcription[1]. |
| References |
[1]. Selective PPARδ Modulators Improve Mitochondrial Function: Potential Treatment for Duchenne Muscular Dystrophy (DMD). ACS Med Chem Lett. 2018 Jul 31;9(9):935-940. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~43.3 mg/mL (~90.9 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.17 mg/mL (4.55 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 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: ≥ 2.17 mg/mL (4.55 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 21.7 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 | 2.0987 mL | 10.4934 mL | 20.9868 mL | |
| 5 mM | 0.4197 mL | 2.0987 mL | 4.1974 mL | |
| 10 mM | 0.2099 mL | 1.0493 mL | 2.0987 mL |