| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 500mg | |||
| Other Sizes |
| Targets |
MC1 receptor (Ki = 18.6 ± 3.3 nM) [1]
MC3 receptor (Ki = 5.45 ± 2.06 nM) [1] MC4 receptor (Ki = 0.29 ± 0.14 nM) [1] MC5 receptor (Ki = 3.29 ± 1.15 nM) [1] HS024 targets the melanocortin receptors, with high selectivity for the MC4 receptor. It acts as a potent antagonist, blocking the activation of MC4 by endogenous melanocortin peptides. Its binding affinities (Ki) for the different melanocortin receptor subtypes are: MC4 (0.29 nM), MC5 (3.29 nM), MC3 (5.45 nM), and MC1 (18.6 nM). This selectivity profile, particularly the high affinity for MC4, makes it a valuable tool for studying MC4 receptor function. |
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| ln Vitro |
Acetyl-(Cys3,Nle4,Arg5,D-2-Nal7,Cys11)-α-MSH (3-11) amide (HS024) did not affect cAMP levels in COS-1 cells expressing human MC1, MC3, MC4, or MC5 receptors at concentrations up to 100 μM. However, at 0.1 μM it completely blocked the cAMP increase induced by αMSH (10 nM for MC1, 100 nM for MC3 and MC4, 1 μM for MC5) in all four receptor-expressing cells. [1]
In vitro, HS024 demonstrates potent and selective antagonism at the MC4 receptor. It exhibits a Ki value of 0.29 nM for the MC4 receptor. It also shows binding to MC5 (Ki = 3.29 nM), MC3 (Ki = 5.45 nM), and MC1 (Ki = 18.6 nM). This cyclic MSH analog shows about 20-fold selectivity for MC4 over other melanocortin receptor subtypes, confirming its utility as a selective MC4 receptor antagonist. |
| ln Vivo |
Intracerebroventricular (icv) injection of Acetyl-(Cys3,Nle4,Arg5,D-2-Nal7,Cys11)-α-MSH (3-11) amide (HS024) in free-feeding rats caused strong dose-dependent stimulation of feeding. At 1 nmol, maximal 4-fold increase in food intake (cumulative ~6-8 g by 4 h). Significant effects: at 1 h only 1 nmol increased intake; at 2,3,4 h all doses (0.1, 0.33, 1.0 nmol) increased intake. Increase comparable to 24h food-deprived rats. [1]
In elevated plus-maze tests (20 min after icv, 0.02 & 0.1 nmol), no differences in maze exploration vs. saline: % open arm entries and % time on open arms unchanged. [1] In open-field tests (immediately after plus-maze), HS024 did not affect horizontal (cells crossed) or vertical (rearing) activity. Fecal boli increased only at 0.02 nmol in plus-maze but not open-field. [1] In vivo, HS024 has been shown to increase food intake. This effect is a direct consequence of MC4 receptor blockade, as the MC4 receptor is a critical anorexigenic (appetite-suppressing) pathway. By antagonizing this receptor, HS024 removes the inhibitory signal on feeding, leading to increased food consumption. This in vivo activity confirms the role of the MC4 receptor in the central regulation of appetite and energy balance. |
| Enzyme Assay |
Competitive binding: COS-1 cells transiently expressing human MC1, MC3, MC4, or MC5 receptors were washed, distributed into 96-well plates, centrifuged, and buffer removed. Cells were incubated for 2 h at 37°C with constant 125I-NDP-MSH and varying unlabeled HS024. After washing with ice-cold buffer, cells were detached with 0.1 N NaOH and radioactivity counted. Data analyzed by computer modeling using mass action laws. Kd values for 125I-NDP-MSH from prior studies. Assays in duplicate, repeated three times. Ki values calculated. [1]
cAMP assay: Transfected COS-1 cells (expressing MC1,3,4,5) were harvested and incubated for 30 min at 37°C in serum-free medium containing 0.5 mM isobutylmethylxanthine with αMSH or HS024. cAMP extracted with perchloric acid (0.4 M final), neutralized, and quantified by protein-binding method using 3H-cAMP and bovine adrenal binding protein (4°C, 150 min). Harvested by filtration on GF/B filters, rinsed, and scintillation counted. HS024 up to 100 μM did not affect basal cAMP; 0.1 μM HS024 completely blocked αMSH-induced cAMP at all four receptors. [1] In vitro receptor binding assays for HS024 are performed to determine its affinity for melanocortin receptors (MC1, MC3, MC4, MC5). Standard protocols involve competitive binding experiments using membrane preparations from cells overexpressing the respective human melanocortin receptors. Radiolabeled, high-affinity melanocortin ligands, such as [125I]-NDP-α-MSH, are used as tracers. Increasing concentrations of HS024 are incubated with the receptor membranes, and the displacement of the tracer is measured. The Ki values for each receptor subtype are calculated from the competition curves. |
| Cell Assay |
In vitro cellular assays for HS024 are conducted using cell lines that express melanocortin receptors, such as HEK293 cells transfected with MC4R. Cells are seeded and incubated with various concentrations of HS024, followed by stimulation with a known agonist like α-MSH. The functional antagonism is measured by quantifying the inhibition of agonist-stimulated cAMP production, a downstream effect of melanocortin receptor activation. The IC50 for this functional inhibition is determined from the dose-response curve, confirming HS024's antagonistic activity.
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| Animal Protocol |
Male Wistar rats (330-380 g) anesthetized with chloral hydrate (350 mg/kg, ip). Stereotaxic implantation of 11-mm 23-gauge cannula into lateral ventricle (coordinates: 0.7 mm posterior to bregma, 1.4 mm lateral, 3.2 mm below skull). Anchored with screws and acrylic, closed with xstylet. 7-day recovery. HS024 dissolved in saline, administered via 31-gauge injector (1.5 mm beyond guide tip) connected to 50-μl syringe with polyethylene tubing. Infusion at 10 μl/min using pump. Needle left 15 sec. Injections between 1200-1600 h every third day, randomized. [1]
Feeding: Food removed; rats injected icv with HS024 (0.1,0.33,1.0 nmol in 5 μl) and returned to home cage. Seven preweighed pellets (~20 g) on clean plastic dishes. Food intake measured at 1,2,3,4 h by weighing remaining pellets and spillage. [1] Elevated plus-maze & open-field: Icv injection of HS024 (0.02,0.1 nmol) or vehicle 20 min before test. Plus-maze: two open arms (50x10 cm) and two closed arms (same size with 40 cm walls), central area 10x10 cm, 65 cm high. Rats placed in novel environment for 5 min, then central area facing open arm; 4-min recording of open/closed arm entries, time on open arms, line crossings. Then open-field: wooden arena (100x100 cm, 40 cm walls) divided into 16 squares; 4-min recording of squares visited (all four paws) and rearing. [1] In vivo animal studies for HS024 typically involve administering the peptide to rodents, often via intracerebroventricular (ICV) injection to target the central nervous system. Following administration, food intake is monitored over a defined period. The orexigenic effect of HS024 is assessed by comparing the food consumption of treated animals to that of vehicle-treated controls. These studies have consistently shown that HS024 increases food intake, demonstrating that blockade of the MC4 receptor is an effective way to stimulate feeding. |
| ADME/Pharmacokinetics |
Specific pharmacokinetic data for HS024 are not detailed in standard references. As a cyclic peptide, it is expected to have improved stability compared to linear peptides but is still likely subject to proteolytic degradation. Its effects after central administration suggest it can act locally in the brain. Its bioavailability and half-life would be important parameters for its use in vivo, and formulation strategies may be needed to enhance its stability and delivery.
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| Toxicity/Toxicokinetics |
Intracerebroventricular injection of Acetyl-(Cys3,Nle4,Arg5,D-2-Nal7,Cys11)-α-MSH (3-11) amide (HS024) at higher doses (0.3 and 1.0 nmol) induced side effects: 1/9 rats at 0.3 nmol and 1/10 rats at 1.0 nmol developed exophthalmus and barrel-rolling (rotation along long axis of body). No lethality observed. [1]
Spillage behavior increased by HS024 (0.33 and 1.0 nmol), but % spillage/CFI (cumulative food intake at 4 h) was not significantly affected. [1] Comprehensive toxicology data for HS024 are not typically reported, as it is a research tool. Its toxicological profile is expected to be related to its pharmacological effects on appetite regulation. High doses could potentially lead to excessive food intake and associated metabolic disturbances, such as obesity. As a selective antagonist, off-target effects at other melanocortin receptors are a consideration, but its selectivity for MC4 suggests a favorable profile for studying this specific receptor. |
| References | |
| Additional Infomation |
Acetyl-(Cys3,Nle4,Arg5,D-2-Nal7,Cys11)-α-MSH (3-11) amide (HS024) has a 29-membered atom ring structure with disulfide bridge between Cys residues. Primary structure: cyclic [AcCys3, Nle4, Arg5, D-Nal7, Cys-NH211]α-MSH-(3-11). Has 11-fold higher MC4 affinity (Ki=0.29 nM) than HS014 (3.16 nM). Combination of Arg5 and Nle4 in 29-membered ring yielded superpotent MC4 selectivity. HS024 is antagonist at MC1, MC3, MC4, and MC5 (unlike SHU9119 and HS014 which are agonists at MC1/MC5). MC4 receptor blockade by HS024 is highly effective for inducing feeding. Does not affect anxiety or locomotor activity at feeding-effective doses. [1]
HS024, also known as Acetyl-(Cys3,Nle4,Arg5,D-2-Nal7,Cys11)-α-MSH (3-11) amide, is a selective cyclic melanocortin-4 (MC4) receptor antagonist. It exhibits high affinity for the MC4 receptor with a Ki of 0.29 nM and shows selectivity over MC1, MC3, and MC5 receptors. In vivo, HS024 increases food intake, confirming the role of MC4 receptor blockade in stimulating appetite. It is a valuable research tool for studying the central regulation of feeding, energy homeostasis, and metabolic disorders. It is not an approved drug. |
| Molecular Weight |
1268.51504
|
|---|---|
| Exact Mass |
1265.569
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| CAS # |
212370-59-7
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| Related CAS # |
HS024 TFA
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| PubChem CID |
25081552
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.717
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| LogP |
-1.57
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| Hydrogen Bond Donor Count |
16
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| Hydrogen Bond Acceptor Count |
15
|
| Rotatable Bond Count |
19
|
| Heavy Atom Count |
89
|
| Complexity |
2470
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| Defined Atom Stereocenter Count |
8
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| SMILES |
CCCC[C@H](NC([C@@H](NC(C)=O)CS)=O)C(N[C@H](C(N[C@H](C(N[C@@H](C(N[C@H](C(N[C@H](C(NCC(N[C@H](C(N)=O)CS)=O)=O)CC1=CNC2=CC=CC=C12)=O)CCCNC(N)=N)=O)CC3=CC4=CC=CC=C4C=C3)=O)CC5=CN=CN5)=O)CCCNC(N)=N)=O
|
| InChi Key |
PUOCNCOPVAOMDE-LQXMKOPKSA-N
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| InChi Code |
InChI=1S/C58H79N19O10S2/c1-3-4-14-40-51(82)72-41(16-9-20-65-57(60)61)53(84)77-45(25-37-27-64-31-69-37)55(86)75-43(23-33-18-19-34-11-5-6-12-35(34)22-33)54(85)73-42(17-10-21-66-58(62)63)52(83)76-44(24-36-26-67-39-15-8-7-13-38(36)39)50(81)68-28-48(79)71-46(49(59)80)29-88-89-30-47(56(87)74-40)70-32(2)78/h5-8,11-13,15,18-19,22,26-27,31,40-47,67H,3-4,9-10,14,16-17,20-21,23-25,28-30H2,1-2H3,(H2,59,80)(H,64,69)(H,68,81)(H,70,78)(H,71,79)(H,72,82)(H,73,85)(H,74,87)(H,75,86)(H,76,83)(H,77,84)(H4,60,61,65)(H4,62,63,66)/t40-,41-,42-,43+,44-,45-,46-,47-/m0/s1
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| Chemical Name |
(4R,10S,13S,16R,19S,22S,25S,28R)-28-acetamido-25-butyl-13,22-bis[3-(diaminomethylideneamino)propyl]-19-(1H-imidazol-5-ylmethyl)-10-(1H-indol-3-ylmethyl)-16-(naphthalen-2-ylmethyl)-6,9,12,15,18,21,24,27-octaoxo-1,2-dithia-5,8,11,14,17,20,23,26-octazacyclononacosane-4-carboxamide
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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 | 0.7883 mL | 3.9416 mL | 7.8832 mL | |
| 5 mM | 0.1577 mL | 0.7883 mL | 1.5766 mL | |
| 10 mM | 0.0788 mL | 0.3942 mL | 0.7883 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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