| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
MC4R
Melanocortin-4 receptor (MC4R). HS024 TFA is a cyclic peptide antagonist of MC4R, a G protein-coupled receptor (GPCR) primarily expressed in the central nervous system (hypothalamus). MC4R is a key regulator of energy balance; its activation by alpha-MSH (an agonist) suppresses appetite and increases energy expenditure. HS024 binds to MC4R with high affinity (Ki = 0.47 nM) and blocks the binding of endogenous agonists, thereby inhibiting the downstream Gs/cAMP signaling pathway. By antagonizing MC4R, HS024 increases food intake and reduces energy expenditure. It is highly selective for MC4R over MC3R (Ki >100 nM) and MC5R (Ki >1000 nM). This selectivity makes it a precise tool for dissecting MC4R-mediated physiological effects. |
|---|---|
| ln Vitro |
In vitro, HS024 TFA is a potent and selective MC4R antagonist. In radioligand binding assays using membranes from cells expressing human MC4R, HS024 displaces 125I-NDP-alpha-MSH with a Ki of 0.47 nM. It shows >300-fold selectivity for MC4R over MC3R and MC5R. In functional assays (cAMP accumulation), HS024 (0.1-1000 nM) antagonizes alpha-MSH-induced cAMP production in MC4R-expressing cells, with an IC50 in the low nM range. The compound itself (up to 1 uM) has no agonist activity (i.e., does not increase cAMP), confirming it as a pure antagonist. In neuronal cultures, HS024 (1-100 nM) blocks the anorexigenic effects of alpha-MSH on arcuate nucleus neurons. The peptide is stable in serum for several hours due to its cyclic structure. The TFA salt is water-soluble. No cytotoxicity is observed at concentrations up to 10 uM in neuronal cell lines.
|
| ln Vivo |
In vivo, HS024 TFA is used in rodent models to stimulate food intake and induce obesity. In fasted or satiated rats, intracerebroventricular (i.c.v.) injection of HS024 (0.1-10 ug) dose-dependently increases food intake within 1-4 hours. For example, in male Sprague-Dawley rats, i.c.v. administration of 1 ug HS024 significantly increases cumulative food intake by 50-100% compared to vehicle. The effect lasts for 2-6 hours. Chronic i.c.v. infusion (e.g., 5 ug/day for 7 days) leads to hyperphagia and weight gain. HS024 also blocks the anorectic effects of melanocortin agonists (e.g., MTII). The compound is also active after peripheral administration (i.p. or s.c.), though it may have lower brain penetration. It is used to study the role of MC4R in energy metabolism, sexual function, and cardiovascular regulation. The TFA salt is suitable for i.c.v. injection; dissolve in artificial cerebrospinal fluid (aCSF) or sterile saline. All animal procedures require IACUC approval.
|
| Enzyme Assay |
For non-cellular receptor binding assays, a competitive radioligand binding assay using membranes from MC4R-expressing cells is standard. Prepare membranes from CHO or HEK293 cells stably expressing human MC4R. Incubate membranes (10-50 ug protein/well) with 0.05-0.1 nM 125I-NDP-alpha-MSH and varying concentrations of HS024 TFA (0.001-1000 nM) in binding buffer (50 mM HEPES pH 7.4, 1 mM CaCl2, 5 mM MgCl2, 0.2% BSA, 0.1% bacitracin) for 60-90 min at 25degC. Separate bound and free by rapid filtration through GF/B filters presoaked in 0.3% PEI. Wash filters, count radioactivity. Non-specific binding is determined in the presence of 1 uM NDP-alpha-MSH. Calculate IC50, then Ki using Cheng-Prusoff equation (Ki = 0.47 nM). For selectivity, perform similar assays with MC3R, MC5R, and MC1R membranes. For functional cell-free assays, measure adenylyl cyclase activity in membrane preparations: incubate MC4R membranes with HS024 (0.1-1000 nM) in the presence of alpha-MSH (1 nM) and measure cAMP production by ELISA. The compound should block alpha-MSH-induced cAMP.
|
| Cell Assay |
For cellular functional assays, use HEK293 cells stably expressing MC4R. Seed cells in 96-well plates (2-4×10^4 cells/well) in DMEM with 10% FBS. After 24 h, wash and replace with serum-free DMEM containing 0.5 mM IBMX (phosphodiesterase inhibitor). Incubate for 20 min at 37degC. Add HS024 TFA (0.1-1000 nM) and incubate for 15 min. Then add alpha-MSH (1 nM) and incubate for an additional 30 min. Lyse cells and measure cAMP using an HTRF or chemiluminescence-based kit. Calculate the EC50 for antagonism (typically <10 nM). For agonist activity, treat cells with HS024 alone (0.1-1000 nM) and measure cAMP; no increase should be observed. For receptor internalization assays, use a fluorescently labeled alpha-MSH (FITC-NDP-MSH) and treat with HS024 to assess blocking of agonist-induced internalization. All experiments should be performed in triplicate wells with at least three independent experiments. Control: DMSO (≤0.1%). Positive control: non-selective antagonist SHU9119. The TFA salt is water-soluble; prepare 1 mM stock in water or PBS, store at -20degC.
|
| Animal Protocol |
For in vivo studies, use male Sprague-Dawley rats (250-300 g) with an indwelling cannula in the lateral ventricle (stereotaxic surgery: coordinates -0.8 mm AP, +1.5 mm ML, -3.5 mm DV from bregma). After 7 days recovery, fast animals for 2-4 hours. Dissolve HS024 TFA in artificial cerebrospinal fluid (aCSF) or sterile saline. Inject i.c.v. via the cannula at doses of 0.1, 0.3, 1, 3, 10 ug in 1-2 uL volume over 1-2 min. Control animals receive aCSF alone. Immediately after injection, return rats to their home cages with pre-weighed food. Measure food intake at 1, 2, 4, 6, and 24 hours. HS024 should increase food intake at doses ≥0.3 ug. For peripheral administration, inject intraperitoneally (i.p.) at 1-10 mg/kg. However, i.c.v. is more effective. For chronic studies, use osmotic minipumps (e.g., 7 days, 5 ug/day i.c.v.). Monitor body weight daily. For combination studies, co-inject with MTII (a MC4R agonist) to demonstrate blockade of anorexia. All animal procedures require IACUC approval. The TFA salt is acceptable; adjust pH to 7.0-7.5 if needed. HS024 is well-tolerated at the doses used, with no seizures or motor impairment.
|
| ADME/Pharmacokinetics |
As a cyclic heptapeptide (MW ~1000), HS024 TFA has limited oral bioavailability and a short plasma half-life when administered peripherally due to renal clearance and proteolysis. For i.c.v. administration, the peptide distributes within the ventricular system and brain parenchyma, reaching the hypothalamus. The half-life in the brain is estimated at 1-2 hours. For peripheral administration (i.v.), plasma t1/2 is likely <15 min. The TFA salt does not affect PK. For PK studies, administer HS024 (10 mg/kg, i.v.) to rats, collect blood at 0, 5, 15, 30, 60, 120 min, and quantify by LC-MS/MS. However, for most research applications, PK is not determined. The compound is used acutely for its pharmacological effects.
|
| Toxicity/Toxicokinetics |
No specific toxicity data are available for HS024 TFA. In acute i.c.v. studies in rats at doses up to 10 ug, no overt behavioral toxicity (seizures, barrel rolling, respiratory distress) is observed. At very high doses (100 ug i.c.v.), some transient hypoactivity may occur, but it is reversible. In peripheral administration (i.p. up to 30 mg/kg) in mice, no mortality or severe weight loss is seen. No genotoxicity or carcinogenicity studies exist. The TFA salt is present in low amounts and is not toxic. Standard laboratory safety precautions should be used. HS024 is for research use only; not approved for human or veterinary use.
|
| References | |
| Additional Infomation |
HS024 is a cyclic heptapeptide antagonist of the melanocortin-4 receptor (MC4R), which is a key regulator of energy balance. MC4R is an attractive target for anti-obesity drugs; agonists reduce appetite, while antagonists increase appetite (useful for cachexia). HS024 has high affinity (Ki 0.47 nM) and selectivity for MC4R, making it a superior tool compared to older antagonists like SHU9119 (which also has partial agonist activity). HS024 is a pure antagonist. It is used in studies of feeding behavior, obesity, sexual behavior, and cardiovascular function. The TFA salt is for research only. As of 2026, no MC4R antagonist has been approved for clinical use (some are in development for anorexia/cachexia). HS024 itself is not a drug.
|
| Molecular Formula |
C60H80F3N19O12S2
|
|---|---|
| Molecular Weight |
1380.52
|
| Related CAS # |
HS024;212370-59-7
|
| Appearance |
White to off-white solid powder
|
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
H2O :~50 mg/mL (~36.22 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
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 | 0.7244 mL | 3.6218 mL | 7.2436 mL | |
| 5 mM | 0.1449 mL | 0.7244 mL | 1.4487 mL | |
| 10 mM | 0.0724 mL | 0.3622 mL | 0.7244 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
