| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Melanocortin receptor 4 (MC4R). TCMCB07 TFA is a cyclic nonapeptide and an orally active, brain-penetrating antagonist of MC4R. By blocking the MC4R, it interrupts the signaling pathway that contributes to appetite suppression and cachexia, making it a potential therapeutic approach for the management of cachexia.
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| ln Vitro |
In vitro, TCMCB07 TFA acts as an antagonist of the MC4R, preventing the binding of the natural agonist alpha-melanocyte-stimulating hormone. This antagonism leads to the downstream activation of pathways that increase food intake and reduce catabolism of muscle and fat tissue, counteracting the cachexia phenotype. The TFA salt form enhances the peptide's stability.
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| ln Vivo |
In vivo, TCMCB07 TFA is an orally active and brain-penetrating MC4R antagonist. It has been studied for its role in cachexia, showing the ability to prevent or reverse the loss of body weight and lean body mass in animal models. Oral administration leads to target engagement in the brain, demonstrating its utility for central nervous system applications.
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| Enzyme Assay |
MC4R binding assay: Membranes from cells expressing the human MC4R are incubated with 125I-labeled NDP-MSH (0.05 nM) and increasing concentrations of TCMCB07 TFA (0-1000 nM) in binding buffer (50 mM HEPES, pH 7.4, 5 mM MgCl2, 0.5% BSA) for 90 min at 25degC. Non-specific binding is determined with 1 uM unlabeled NDP-MSH. Bound radioactivity is separated by filtration, and IC50 is calculated.
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| Cell Assay |
Cellular functional assay: MC4R-expressing cells are seeded in 96-well plates. Cells are pre-incubated with TCMCB07 TFA (0-1000 nM) for 15-30 min and then stimulated with a submaximal concentration of the agonist NDP-MSH (1-10 nM). cAMP levels are measured by HTRF or ELISA. Antagonism is assessed as the concentration of TCMCB07 needed to reduce NDP-MSH-induced cAMP accumulation by 50% (IC50).
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| Animal Protocol |
Cachexia mouse model: Male BALB/c or C57BL/6 mice are implanted subcutaneously with C26 colon carcinoma cells to induce cancer cachexia. After tumor establishment, mice are randomized into groups (n=6-8). TCMCB07 TFA is administered orally at doses of 1-30 mg/kg, once or twice daily for 14-21 days. Body weight, food intake, and tumor volume are measured. Muscle (gastrocnemius) and fat pad weights are measured at termination. Plasma cytokine levels are measured by ELISA.
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| ADME/Pharmacokinetics |
As an orally active cyclic peptide, TCMCB07 TFA has favorable oral bioavailability. The peptide resists proteolytic degradation in the gastrointestinal tract due to its cyclic structure. Following oral administration, it crosses the blood-brain barrier to reach its target. Detailed PK parameters in rodents include a half-life of 2-4 h and Cmax reached within 1-2 h. The TFA salt enhances stability.
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| Toxicity/Toxicokinetics |
Toxicity data for TCMCB07 TFA are being evaluated in preclinical studies. As a cyclic peptide MC4R antagonist, potential toxicities may include on-target effects on weight gain, appetite, and metabolism. At high doses, adverse effects could include excessive weight gain, metabolic syndrome, and potential cardiovascular effects. It is intended for research use only and not for human therapeutic use.
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| References | |
| Additional Infomation |
TCMCB07 TFA is a research compound that has not yet received regulatory approval for human therapeutic use. It is a cyclic peptide antagonist of MC4R with oral activity and brain penetration. It is in preclinical development for the treatment of cachexia associated with cancer or chronic kidney disease. For research use only. Store as a powder at -20degC, sealed and away from moisture.
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| Molecular Formula |
C63H87N15O11.XC2HF3O2
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| Molecular Weight |
1230.46 (free base)
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| Related CAS # |
TCMCB07;1456699-27-6
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| Appearance |
White to off-white 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) |
DMSO :≥ 100 mg/mL
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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.) |
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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