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HS 024

* Please kindly note that our products are not to be used for therapeutic purposes and cannot be sold to patients.

HS 024 is a potent melanocortin MC4 receptor antagonist (Ki = 0.29, 18.6, 5.45 and 3.29 nM for cloned human MC4, MC1, MC3 and MC5 receptors, respectively). HS 024 promotes food intake, blocks α-MSH- and MTII-induced hypotension and bradycardia in rats, following central administration in vivo.

Category
Peptide Inhibitors
Catalog number
BAT-015095
CAS number
212370-59-7
Molecular Formula
C58H79N19O10S2
Molecular Weight
1266.52
HS 024
IUPAC 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
Synonyms
Acetyl-(Cys3,Nle4,Arg5,D-2-Nal7,Cys11)-α-MSH (3-11) amide; N-acetyl-L-cysteinyl-L-norleucyl-L-arginyl-L-histidyl-3-(2-naphthyl)-D-alanyl-L-arginyl-L-tryptophyl-glycyl-L-cysteinamide (1->9)-disulfide; Ac-Cys(1)-Nle-Arg-His-D-2Nal-Arg-Trp-Gly-Cys(1)-NH2; HS024; HS-024
Appearance
White Lyophilized Solid
Purity
≥95%
Density
1.50±0.1 g/cm3 (Predicted)
Sequence
C-Nle-RH-2Nal-RWGC (Disulfide bridge: Cys1-Cys9)
Storage
Store at -20°C
Solubility
Soluble in Water
InChI
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
InChI Key
PUOCNCOPVAOMDE-LQXMKOPKSA-N
Canonical SMILES
CCCCC1C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NCC(=O)NC(CSSCC(C(=O)N1)NC(=O)C)C(=O)N)CC2=CNC3=CC=CC=C32)CCCN=C(N)N)CC4=CC5=CC=CC=C5C=C4)CC6=CN=CN6)CCCN=C(N)N
1.Characterization of neuropeptide Y in snakeskin gourami and the change in its expression due to feeding status and melanocortin 4 receptor expression.
Boonanuntanasarn S1, Jangprai A, Yoshizaki G. Gen Comp Endocrinol. 2012 Nov 1;179(2):184-95. doi: 10.1016/j.ygcen.2012.07.024. Epub 2012 Aug 8.
In this study, we characterized the neuropeptide Y (NPY) mRNA in snakeskin gourami (Trichogaster pectoralis) (TpNPY). TpNPY displayed characteristics typical of previously reported NPYs, and it exhibited a high degree of homology with the NPY proteins of other vertebrates. A phylogenetic analysis demonstrated that TpNPY was closely related to the NPYs found in the acanthomorpha and salmoniformes fish species. TpNPY was found to be ubiquitously expressed in all brain regions when assessed by real-time RT-PCR and in situ hybridization. In addition, a graded expression level of TpNPY was observed in peripheral tissues; for example, a moderate level of TpNPY was found in the gills, liver, kidney, stomach, intestine, spleen and gonads, while a low level of TpNPY was found in the muscle. The change in expression of TpNPY with respect to daily feeding habits was investigated in distinct brain regions, including the telencephalon, mesencephalon, metencephalon, and diencephalon.
2.A critical role for the melanocortin 4 receptor in stress-induced relapse to nicotine seeking in rats.
Qi X1, Yamada H, Corrie LW, Ji Y, Bauzo RM, Alexander JC, Bruijnzeel AW. Addict Biol. 2015 Mar;20(2):324-35. doi: 10.1111/adb.12129. Epub 2014 Feb 24.
Tobacco addiction is characterized by a lack of control over smoking and relapse after periods of abstinence. Smoking cessation leads to a dysphoric state that contributes to relapse to smoking. After the acute withdrawal phase, exposure to stressors increases the risk for relapse. Blockade of melanocortin 4 (MC4 ) receptors has anxiolytic and antidepressant-like effects in animal models. The aim of these studies was to investigate the role of MC4 receptors in the dysphoria associated with nicotine withdrawal and stress-induced reinstatement of nicotine seeking. To study stress-induced reinstatement, rats self-administered nicotine for 16 days and then nicotine seeking was extinguished by substituting saline for nicotine. Nicotine seeking was reinstated by intermittent footshock stress. The intracranial self-stimulation (ICSS) procedure was used to assess the negative mood state associated with nicotine withdrawal. Elevations in the ICSS thresholds are indicative of a dysphoric state.
3.Protective effects of melanocortins on short-term changes in a rat model of traumatic brain injury*.
Bitto A1, Polito F, Irrera N, Calò M, Spaccapelo L, Marini HR, Giuliani D, Ottani A, Rinaldi M, Minutoli L, Guarini S, Squadrito F, Altavilla D. Crit Care Med. 2012 Mar;40(3):945-51. doi: 10.1097/CCM.0b013e318236efde.
OBJECTIVE: Treatment for traumatic brain injury remains elusive despite compelling evidence from animal models for a variety of therapeutic targets. Melanocortins have established neuroprotective effects against experimental ischemic stroke. We investigated whether melanocortin treatment of traumatic brain injury induces neuroprotection and promotes functional recovery.
4.Melanocortin MC4 receptor agonists alleviate brain damage in abdominal compartment syndrome in the rat.
Liu D1, Zhang HG1, Zhao ZA2, Chang MT1, Li Y1, Yu J1, Zhang Y1, Zhang LY3. Neuropeptides. 2015 Feb;49:55-61. doi: 10.1016/j.npep.2014.12.003. Epub 2015 Jan 7.
Intra-abdominal hypertension (IAH) is accompanied by high morbidity and mortality in surgical departments and ICUs. However, its specific pathophysiology is unclear. IAH not only leads to intra-abdominal tissue damage but also causes dysfunction in distal organs, such as the brain. In this study, we explore the protective effects of melanocortin 4 receptor agonists in IAH-induced brain injury. The IAH rat models were induced by hemorrhagic shock/resuscitation (with the mean arterial pressure (MAP) maintained at 30 mm Hg for 90 min followed by the reinfusion of the withdrawn blood with lactated Ringer's solution). Then, air was injected into the peritoneal cavity of the rats to maintain an intra-abdominal pressure of 20 mm Hg for 4 h. The effects of the melanocortin 4 receptor agonist RO27-3225 in alleviating the rats' IAH brain injuries were observed, which indicated that RO27-3225 could reduce brain edema, the expressions of the IL-1β and TNF-α inflammatory cytokines, the blood-brain barrier's permeability and the aquaporin4 (AQP4) and matrix metalloproteinase 9 (MMP9) levels.
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