| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
Sodium-coupled citrate transporter (NaCT, also known as SLC13A5), which mediates the cellular uptake of citrate from the extracellular space. PF-06649298 binds to NaCT, inhibiting citrate transport and thereby modulating downstream metabolic pathways.
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| ln Vitro |
PF-06649298 (0-100 μM; 30 minutes) prevents citrate from being absorbed by cells [1].
PF-06649298 specifically interacts with NaCT and inhibits citrate transport in human hepatocytes with an IC50 of 16.2 microM. In HEK293 cells overexpressing NaCT, it inhibits citrate uptake with an IC50 of 0.41 microM. By blocking citrate entry into cells, it reduces de novo lipogenesis and modulates glucose metabolism. |
| 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].
PF-06649298 (250 mg/kg, oral, twice daily for 21 days) reverses glucose intolerance in mice fed a high-fat diet. It is being investigated for the regulation of glucose metabolism and lipid metabolism, with potential applications in metabolic diseases such as type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and obesity. |
| Enzyme Assay |
Recombinant NaCT-expressing HEK293 cell membranes (5-20 microg) are incubated with PF-06649298 (0.001-100 microM) and 14C-citrate (10-50 microM) in uptake buffer (25 mM HEPES-Tris, pH 7.4, 140 mM NaCl, 5.4 mM KCl, 1.8 mM CaCl2, 0.8 mM MgSO4) at 37degC for 5-15 minutes. Uptake is terminated by ice-cold wash buffer, and radioactivity is measured by scintillation counting.
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| 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. HEK293 cells stably expressing human NaCT are seeded in 96-well plates. PF-06649298 (0.01-100 microM) is added 15-30 minutes prior to addition of 14C-citrate (10-50 microM). After 5-15 minutes, cells are washed, lysed, and intracellular radioactivity is measured. IC50 is calculated from dose-response curves. |
| 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. Mice on a high-fat diet are orally administered PF-06649298 (250 mg/kg, twice daily) for 21 days. Glucose tolerance is assessed by intraperitoneal glucose tolerance test (IPGTT, 1-2 g/kg glucose). Blood glucose is measured at 0, 15, 30, 60, 90, 120 minutes post-glucose challenge. Plasma insulin, triglycerides, and free fatty acids are measured by ELISA and colorimetric assays. |
| ADME/Pharmacokinetics |
No detailed PK data; PF-06649298 is orally bioavailable. In rodents, oral administration likely achieves a Cmax of 10-50 microM at 1-2 hours post-dose, with a terminal half-life of 2-4 hours. High plasma protein binding (>90%) is predicted based on its lipophilic properties.
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| Toxicity/Toxicokinetics |
No formal toxicity data. In mice, PF-06649298 is well-tolerated at 250 mg/kg (oral) for 21 days with no observed body weight loss, hepatotoxicity, or nephrotoxicity. No significant adverse effects on serum chemistry parameters have been reported in preclinical studies.
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| References |
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| Additional Infomation |
SLC13A5 inhibitor; structure can be found in the first article.
PF-06649298 is a research compound only, not FDA-approved. It is a valuable tool for studying the role of NaCT (SLC13A5) in citrate homeostasis, de novo lipogenesis, and insulin resistance. NaCT is a potential therapeutic target for the treatment of metabolic syndrome, NAFLD, and type 2 diabetes. |
| Molecular Formula |
C16H22O5
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|---|---|
| Molecular Weight |
294.342885494232
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| Exact Mass |
294.146
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| CAS # |
1854061-16-7
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| PubChem CID |
127029348
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
21
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| Complexity |
377
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C(C)(C)(C1C=CC(CC[C@@](CC(O[H])=O)(C(O)=O)O)=CC=1)C
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| InChi Key |
QNFWRHKLBLSSPB-MRXNPFEDSA-N
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| 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
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| Chemical Name |
(2R)-2-[2-(4-tert-butylphenyl)ethyl]-2-hydroxybutanedioic acid
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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 |
| 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 (~339.74 mM)
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|---|---|
| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (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 |
*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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