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| 1mg |
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| Other Sizes |
| Targets |
The unlabeled compound, CMPF (3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid), has well-characterized biological targets. It is a potent inhibitor of organic anion transporters (OATs), specifically OAT1 and OAT3, which are responsible for the renal secretion of various endogenous and exogenous compounds. By inhibiting these transporters, elevated levels of CMPF can lead to the accumulation of uremic toxins in the blood, contributing to the pathophysiology of chronic kidney disease (CKD). Additionally, CMPF has been shown to bind to thyroxine-binding globulin (TBG) and displace T4, affecting thyroid hormone transport. It also inhibits the transport of thyroid hormones into hepatocytes. CMPF-d5, being the labeled analog, interacts with the same proteins and is used as a tracer to study these interactions.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
The in vitro biological activity of CMPF-d5 has not been independently studied, but its unlabeled counterpart, CMPF, shows potent inhibitory effects on OATs. In vitro studies using transfected cells overexpressing human OAT1 and OAT3 have shown that CMPF inhibits the uptake of model substrates like PAH (p-aminohippurate) and ES (estrone sulfate) with IC₅0 values in the low micromolar range (1-10 uM). Furthermore, in rat hepatocyte suspensions, CMPF has been demonstrated to inhibit the cellular uptake of T4 (thyroxine). This inhibition is non-competitive and reversible. In addition to transporter inhibition, CMPF exhibits pro-inflammatory properties, such as inducing the expression of pro-inflammatory cytokines (e.g., TNF-alpha, IL-6) in cultured human proximal tubule cells. CMPF-d5 is primarily used as an internal standard to quantify these effects accurately. |
| ln Vivo |
In vivo studies with the unlabeled compound CMPF have revealed its role as an endogenous uremic toxin. In animal models, such as rats with chronic kidney disease (CKD), systemic administration of CMPF leads to its accumulation in the blood. This accumulation correlates with reduced renal function, specifically a decrease in the clearance of other uremic toxins, by inhibiting organic anion transporters (OATs). In rats, elevated CMPF levels have been associated with increased oxidative stress and inflammation in the kidney tissue. Furthermore, CMPF has been shown to inhibit the cellular uptake of T4 in the liver, disrupting thyroid hormone metabolism in vivo. CMPF-d5 is used as an internal standard in these studies to accurately quantify endogenous CMPF levels and track its biodistribution following exogenous administration, providing a precise measure of toxin exposure.
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| Enzyme Assay |
A standard non-cell-based assay for CMPF-d5 involves the measurement of its inhibitory effect on organic anion transporter (OAT) activity using membrane vesicles. For this protocol, prepare membrane vesicles from HEK293 cells stably expressing human OAT1. Dilute the vesicles in a buffer containing 100 mM KCl, 10 mM HEPES (pH 7.4). Prepare a reaction mixture containing 1 uM of a fluorescent model substrate (e.g., 6-carboxyfluorescein) and increasing concentrations of unlabeled CMPF (0.1 uM to 100 uM). Initiate the transport reaction by adding 20 uL of the vesicle suspension (approx. 50 ug protein) to 80 uL of the substrate-CMPF mixture. Incubate the mixture at 25degC for 2-5 minutes. Terminate the reaction by adding 1 mL of ice-cold stop buffer (100 mM KCl, 10 mM HEPES). Immediately vacuum-filter the samples through a 0.45 um nitrocellulose filter. Wash the filter twice with stop buffer. Extract the accumulated fluorescence from the filter using an appropriate solvent and measure using a fluorescence plate reader. Calculate the half-maximal inhibitory concentration (IC₅0) from the dose-response curve. Use CMPF-d5 as an LC-MS internal standard to validate CMPF concentrations in the assay mixture.
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| Cell Assay |
A standard in vitro cell-based protocol for the unlabeled CMPF involves its use in studying OAT inhibition in a renal cell line. Culture HEK293 cells stably transfected with human OAT3 in DMEM supplemented with 10% FBS and antibiotics at 37degC with 5% CO2. Seed the cells in 24-well plates pre-coated with poly-L-lysine at a density of 1×10⁵ cells/well and allow them to grow for 48 hours. On the day of the assay, wash the cells twice with pre-warmed HBSS buffer. Pre-incubate the cells with varying concentrations (0.1 uM to 100 uM) of unlabeled CMPF in HBSS for 15 minutes. Remove the pre-incubation solution and add a transport solution containing 1 uM of the model substrate, [3H]-estrone sulfate (ES), along with the same concentration of CMPF used in pre-incubation. Incubate for 5 minutes at 37degC. Terminate the uptake by washing the cells three times with ice-cold HBSS. Lyse the cells with 0.1 N NaOH and quantify the accumulated radioactivity by liquid scintillation counting. Use CMPF-d5 as an internal standard in LC-MS analysis to confirm the drug exposure concentrations in the cell culture media.
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| Animal Protocol |
A representative in vivo animal experimental protocol for CMPF-d5 involves a chronic kidney disease model. Use male Sprague-Dawley rats (250-300g) rendered uremic via 5/6 nephrectomy. After 4 weeks of recovery, treat the uremic rats and sham-operated controls with daily intraperitoneal injections of unlabeled CMPF (10 mg/kg) or vehicle (saline) for 2 weeks. Before and after treatment, collect 24-hour urine samples using metabolic cages. At the end of the study, anesthetize the animals and collect blood via cardiac puncture. Harvest major organs including liver, kidney, and heart. Measure serum creatinine and BUN levels to assess renal function. Process plasma, urine, and tissue homogenates by protein precipitation using acetonitrile. Add CMPF-d5 as an internal standard to each sample. Analyze samples using LC-MS/MS to quantify CMPF concentrations and relate them to renal functional parameters, oxidative stress markers, and inflammatory cytokine levels. This allows the establishment of the pharmacokinetic-pharmacodynamic relationship of the uremic toxin.
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| ADME/Pharmacokinetics |
The pharmacokinetics of CMPF-d5 have not been directly studied, but the PK of its unlabeled form, CMPF, is well-documented. In humans, CMPF is produced endogenously and is normally present in the blood at concentrations of 0.5-2 uM in healthy individuals. However, in patients with chronic kidney disease (CKD), serum CMPF levels can accumulate to concentrations as high as 200 uM. In animal studies, intravenously administered CMPF has a rapid initial distribution phase followed by a slow elimination phase. The compound exhibits high protein binding (>99%), specifically to albumin, which reduces its volume of distribution and prolongs its elimination half-life to over 24 hours in the presence of renal impairment. CMPF is primarily eliminated through the kidneys via active secretion by OATs, a process that is impaired in CKD. CMPF-d5 is used as an internal standard for measuring these parameters.
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| Toxicity/Toxicokinetics |
The toxicological profile of CMPF-d5 is not established, but it is a derivative of the endogenous uremic toxin CMPF (3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid). In patients with chronic kidney disease (CKD), elevated levels of CMPF (up to 200 uM) are associated with the progression of renal fibrosis and an increased risk of cardiovascular disease. CMPF has been shown to inhibit mitochondrial function and induce oxidative stress in renal tubular cells, leading to cell apoptosis. Furthermore, it disrupts normal thyroid hormone homeostasis by inhibiting the binding of T4 to thyroxine-binding globulin and interfering with hepatocyte T4 uptake. The compound is also implicated in the development of insulin resistance. Due to its ability to inhibit OATs, it may cause significant drug-drug interactions by reducing the clearance of co-administered drugs. Normal laboratory safety precautions should be taken when handling CMPF-d5.
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| References | |
| Additional Infomation |
CMPF-d5 is the stable isotope-labeled version (deuterium-labeled) of CMPF (3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid), an endogenous furan fatty acid metabolite. It is used as an internal standard for the precise quantitation of CMPF in biological samples by LC-MS. CMPF is a uremic toxin that accumulates in the blood of patients with chronic kidney disease (CKD). It is an inhibitor of organic anion transporters (OAT1 and OAT3) and can displace thyroid hormones from their binding proteins. Elevated levels of CMPF have been associated with several pathological conditions including CKD progression, cardiovascular disease, and insulin resistance. Because it is a dietary-derived metabolite (found in fish oil), its levels can be influenced by diet. CMPF-d5 is an essential tool for clinical research and drug development to understand the role of uremic toxins in disease pathology.
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| Molecular Formula |
C12H11D5O5
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|---|---|
| Molecular Weight |
245.28
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| Exact Mass |
245.131
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| CAS # |
2749807-07-4
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| Related CAS # |
CMPF;86879-39-2
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| PubChem CID |
137699791
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
17
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| Complexity |
289
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(=C(OC(CCC(O)=O)=C1C(=O)O)CC(C([2H])([2H])[2H])([2H])[2H])C
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| InChi Key |
WMCQWXZMVIETAO-WNWXXORZSA-N
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| InChi Code |
InChI=1S/C12H16O5/c1-3-4-8-7(2)11(12(15)16)9(17-8)5-6-10(13)14/h3-6H2,1-2H3,(H,13,14)(H,15,16)/i1D3,3D2
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| Chemical Name |
2-(2-carboxyethyl)-4-methyl-5-(2,2,3,3,3-pentadeuteriopropyl)furan-3-carboxylic 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 4.0770 mL | 20.3849 mL | 40.7697 mL | |
| 5 mM | 0.8154 mL | 4.0770 mL | 8.1539 mL | |
| 10 mM | 0.4077 mL | 2.0385 mL | 4.0770 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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