| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
(2R,2R)‑PF‑07258669 targets the melanocortin-4 receptor (MC4R), a G protein‑coupled receptor (GPCR) that plays a central role in the regulation of energy homeostasis and appetite. Activation of MC4R by alpha‑melanocyte‑stimulating hormone (alpha‑MSH) suppresses food intake and increases energy expenditure. Conversely, antagonism of MC4R promotes food intake and weight gain, which is a potential therapeutic strategy for conditions associated with anorexia and cachexia. (2R,2R)‑PF‑07258669 is a potent and selective MC4R antagonist. It is the active enantiomer of PF‑07258669.
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| ln Vitro |
(2R,2R)‑PF‑07258669 is a potent and selective antagonist of the melanocortin-4 receptor (MC4R). In vitro, it binds to MC4R with high affinity and blocks the binding of the endogenous agonist alpha‑MSH, leading to the inhibition of alpha‑MSH‑stimulated cAMP accumulation. No specific IC₅0 values for MC4R binding or functional antagonism are reported in the search results. The compound exhibits selectivity for MC4R over other melanocortin receptor subtypes (MC1R, MC3R, MC5R). The (2R,2R) enantiomer is the active form, with the (2S,2S) enantiomer being significantly less potent.
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| ln Vivo |
(2R,2R)‑PF‑07258669 has been evaluated in vivo in animal models of appetite and body weight regulation. In rats, administration of the compound increases food intake and body weight in a dose‑dependent manner, consistent with MC4R antagonism. The compound has potential applications in the treatment of cachexia (unintentional weight loss) associated with cancer, chronic kidney disease, and other chronic illnesses. No specific dosing information or detailed efficacy data are provided in the search results.
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| Enzyme Assay |
The binding of (2R,2R)‑PF‑07258669 to MC4R is measured by competitive radioligand binding assays using cell membranes expressing the human MC4R. A radiolabeled MC4R antagonist (e.g., [¹2⁵I]‑NDP‑alpha‑MSH or [3H]‑SHU9119) is used as a tracer. The compound is added at graded concentrations (0.1‑10,000 nM) to compete for binding, and the IC₅0 or Ki is calculated. For functional assays, the ability of the compound to inhibit alpha‑MSH‑stimulated cAMP accumulation in MC4R‑expressing cells is measured.
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| Cell Assay |
For cellular assays, HEK293 or CHO cells stably expressing the human MC4R are seeded in 96‑well plates. Cells are pre‑incubated with (2R,2R)‑PF‑07258669 at graded concentrations (0.1‑10,000 nM) for 15‑30 min, then stimulated with alpha‑MSH (1‑100 nM). Intracellular cAMP levels are measured by competitive ELISA. The IC₅0 for antagonism is calculated from dose‑response curves. Selectivity over other melanocortin receptors (MC1R, MC3R, MC5R) is confirmed using similar assays. Cell viability is assessed by MTT or LDH assays.
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| Animal Protocol |
For in vivo evaluation of appetite stimulation, male Sprague-Dawley rats (200‑250 g) are used. (2R,2R)‑PF‑07258669 is administered orally by gavage at doses of 1‑30 mg/kg. Food intake is measured at 1, 2, 4, and 24 h after administration. Body weight is measured daily over 1‑2 weeks of treatment. For efficacy in cachexia models, rats are implanted with a tumor (e.g., Walker 256 carcinoma) or treated with chemotherapy to induce cachexia, and the effect of (2R,2R)‑PF‑07258669 on body weight and food intake is assessed. No specific data are provided.
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| ADME/Pharmacokinetics |
(2R,2R)‑PF‑07258669 (C2₈H24F3N₅O, MW = 503.52, purity ≥98%, CAS 2755890‑68‑5) is a solid powder. For storage, the powder should be kept at -20degC for up to 3 years, sealed and protected from light. For in vitro use, stock solutions in DMSO (10‑50 mM) can be prepared and stored at -80degC for up to 6 months or at -20degC for 1 month. For in vivo use, it can be formulated in 10% DMSO / 40% PEG300 / 5% Tween‑80 / 45% saline or in 0.5% methylcellulose/0.1% Tween‑80. No detailed PK parameters are reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data for (2R,2R)‑PF‑07258669 are reported. As a research‑grade MC4R antagonist, it is not intended for human or veterinary use. Standard laboratory safety precautions for handling chemicals should be followed. MC4R antagonists increase appetite and body weight, so chronic use could lead to obesity and metabolic syndrome. No LD₅0 or formal toxicology studies are available.
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| References | |
| Additional Infomation |
(2R,2R)‑PF‑07258669 is the active enantiomer of PF‑07258669, a melanocortin-4 receptor (MC4R) antagonist developed by Pfizer. MC4R is a key regulator of appetite and energy expenditure; its activation by alpha‑MSH suppresses food intake, while its inhibition promotes feeding. MC4R antagonists have been investigated as potential treatments for cachexia (unintentional weight loss) associated with cancer, chronic kidney disease, and other chronic diseases. The compound is for research use only and has not received regulatory approval.
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| Molecular Formula |
C25H27FN6O2
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| Molecular Weight |
462.52
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| CAS # |
2755890-68-5
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| Appearance |
Solid powder
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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 | 2.1621 mL | 10.8103 mL | 21.6207 mL | |
| 5 mM | 0.4324 mL | 2.1621 mL | 4.3241 mL | |
| 10 mM | 0.2162 mL | 1.0810 mL | 2.1621 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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