| Size | Price | Stock | Qty |
|---|---|---|---|
| 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] |
|---|---|
| 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]
|
| 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] |
| 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] |
| 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] |
| 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] |
| 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]
|
| Molecular Weight |
1268.51504
|
|---|---|
| Exact Mass |
1265.569
|
| CAS # |
212370-59-7
|
| Related CAS # |
HS024 TFA
|
| PubChem CID |
25081552
|
| Appearance |
Typically exists as solid at room temperature
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| Density |
1.5±0.1 g/cm3
|
| Index of Refraction |
1.717
|
| LogP |
-1.57
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| Hydrogen Bond Donor Count |
16
|
| Hydrogen Bond Acceptor Count |
15
|
| Rotatable Bond Count |
19
|
| Heavy Atom Count |
89
|
| Complexity |
2470
|
| Defined Atom Stereocenter Count |
8
|
| 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
|
| 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
|
| 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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