Physicochemical Properties
| Molecular Formula | C16H22O5 |
| Molecular Weight | 294.342885494232 |
| Exact Mass | 294.146 |
| CAS # | 1854061-16-7 |
| PubChem CID | 127029348 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 2.5 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 21 |
| Complexity | 377 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | C(C)(C)(C1C=CC(CC[C@@](CC(O[H])=O)(C(O)=O)O)=CC=1)C |
| InChi Key | QNFWRHKLBLSSPB-MRXNPFEDSA-N |
| InChi Code | InChI=1S/C16H22O5/c1-15(2,3)12-6-4-11(5-7-12)8-9-16(21,14(19)20)10-13(17)18/h4-7,21H,8-10H2,1-3H3,(H,17,18)(H,19,20)/t16-/m1/s1 |
| Chemical Name | (2R)-2-[2-(4-tert-butylphenyl)ethyl]-2-hydroxybutanedioic acid |
| 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
| ln Vitro | PF-06649298 (0-100 μM; 30 minutes) prevents citrate from being absorbed by cells [1]. |
| ln Vivo | In mice given a high-fat diet (HFD), PF-06649298 (250 mg/kg; orally twice daily; for 21 days) reverses glucose intolerance [2]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: HEK-293 cells, human hepatocytes and mouse hepatocytes expressing NaCT, NaDC1 or NaDC3 Tested Concentrations: 0-100 μM Incubation Duration: 30 minutes Experimental Results: Shows NaCT relative to dicarboxylic acid transport Selectivity of proteins NaDC1 and NaDC3. Inhibits citrate uptake in HEK-293 cells, human hepatocytes, and mouse hepatocytes expressing NaCT, NaDC1, or NaDC3 with IC50 of 408 nM, >100 μM, >100 μM, 16.2 μM, and 4.5 μM, respectively. |
| Animal Protocol |
Animal/Disease Models: High-fat diet (HFD) mice [2] Doses: 250 mg/kg Route of Administration: po (oral gavage); 250 mg/kg, twice (two times) daily; for 21 days Experimental Results: Plasma glucose, liver function of HFD mice Triglycerides, diglycerides, and hepatic acylcarnitine concentrations are diminished. Completely reversed glucose intolerance in HFD mice. |
| References |
[1]. Optimization of a Dicarboxylic Series for in Vivo Inhibition of Citrate Transport by the Solute Carrier 13 (SLC13) Family. J Med Chem. 2016 Feb 11;59(3):1165-75. [2]. Discovery and characterization of novel inhibitors of the sodium-coupled citrate transporter (NaCT or SLC13A5). Sci Rep. 2015 Dec 1;5:17391. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~339.74 mM) |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3974 mL | 16.9872 mL | 33.9743 mL | |
| 5 mM | 0.6795 mL | 3.3974 mL | 6.7949 mL | |
| 10 mM | 0.3397 mL | 1.6987 mL | 3.3974 mL |