HS014 TFA |
Catalog No.GC63724
One-Click Copy Product Info
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HS014 TFA is a potent and selective melanocortin MC4 receptor antagonist (Ki=3.16nM).
Products are for research use only. Not for human use. We do not sell to patients.
Sample solution is provided at 25 µL, 10mM.
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HS014 TFA is a potent and selective melanocortin MC4 receptor antagonist (Ki=3.16nM). HS014 TFA regulates appetite and energy balance by blocking the interaction between the MC4 receptor and endogenous ligands, while also reducing inflammatory responses by inhibiting IL-1β-induced Fos expression[1-2]. HS014 TFA is utilized in research related to obesity, diabetes, and metabolic syndrome[3-4].
In vitro, epidermal melanocytes were pretreated with HS014 TFA (10nM–200nM) for 30 minutes, followed by stimulation with β-MSH (200nM) or the N-terminally modified α-MSH analog NDP-α-MSH (200nM) for 72 hours. HS014 TFA significantly inhibited melanin formation and reduced cAMP production[5]. MC4R-overexpressing M1830 astrocytoma cells were treated with HS014 TFA (1nM) for 12 days. This treatment significantly downregulated the expression of p-JNK, ATF3, and c-Jun proteins, while also suppressing the activation of the JNK signaling pathway[6].
In vivo, HS014 TFA (1μg; 5μl) was administered via a single intracerebroventricular (icv) injection in rats that had been previously induced with fever by lipopolysaccharide (LPS; 30μg/kg; i.p.). HS014 TFA had no significant effect on the febrile response but completely blocked the antipyretic effect produced by the selective MC4R agonist MRLOB-0001 (150ng; icv)[7]. HS014 TFA (3.5ng or 100μg, intranasal infusion) was administered as a single dose 30 minutes before a single prolonged stress (SPS) exposure in rats. The 100μg dose significantly reduced the elevation in plasma corticosterone levels measured 30 minutes after the SPS stressor ended, while both doses prevented the stress-induced short-term increase in corticotropin-releasing hormone (CRH) mRNA levels in the basal medial hypothalamus, as well as the increase in tyrosine hydroxylase (TH) and dopamine-β-hydroxylase (DBH) mRNA levels in the locus coeruleus[8].
References:
[1] Schiöth HB, Mutulis F, Muceniece R, et al. Discovery of novel melanocortin4 receptor selective MSH analogues. Br J Pharmacol. 1998 May;124(1):75-82.
[2] Ercil NE, Galici R, Kesterson RA. HS014, a selective melanocortin-4 (MC4) receptor antagonist, modulates the behavioral effects of morphine in mice. Psychopharmacology (Berl). 2005 Jul;180(2):279-85.
[3] Kask A, Rägo L, Mutulis F, et al. Selective antagonist for the melanocortin 4 receptor (HS014) increases food intake in free-feeding rats. Biochem Biophys Res Commun. 1998 Apr 7;245(1):90-3.
[4] Gao Z, Lei D, Welch J, et al. Agonist-dependent internalization of the human melanocortin-4 receptors in human embryonic kidney 293 cells. J Pharmacol Exp Ther. 2003 Dec;307(3):870-7.
[5] Spencer JD, Schallreuter KU. Regulation of pigmentation in human epidermal melanocytes by functional high-affinity beta-melanocyte-stimulating hormone/melanocortin-4 receptor signaling. Endocrinology. 2009 Mar;150(3):1250-8.
[6] Zhao Y, Xin Y, Chu H. MC4R Is Involved in Neuropathic Pain by Regulating JNK Signaling Pathway After Chronic Constriction Injury. Front Neurosci. 2019 Sep 10;13:919.
[7] Loopuijt LD. Local application of L- threo-hydroxyaspartate and malonate in rats in vivo induces rigidity and damages neurons of the substantia nigra, pars compacta. J Neural Transm (Vienna). 2002 Oct;109(10):1275-94.
[8] Serova LI, Laukova M, Alaluf LG, et al, Blockage of melanocortin-4 receptors by intranasal HS014 attenuates single prolonged stress-triggered changes in several brain regions. J Neurochem. 2014 Dec;131(6):825-35.
| Cell experiment [1]: | |
Cell lines | Epidermal melanocytes and Keratinocytes |
Preparation Method | Epidermal melanocytes and keratinocytes (phototype III) were seeded in six-well plates and pre-incubated in medium lacking supplemented tetradecanoylphorbol acetate for 48 hours. Before stimulation, the specific MC4-R antagonist HS014 TFA (10nM-200nM) was added to the appropriate wells. |
Reaction Conditions | 10nM-200nM; 30min. |
Applications | HS014 TFA significantly attenuated the induction of melanin formation in melanocytes stimulated by β-MSH or NDP-α-MSH over 72 hours. In both melanocytes and keratinocytes, HS014 TFA attenuated the cAMP response induced by β-MSH or NDP-α-MSH after 1 hour of stimulation. |
| Animal experiment [2]: | |
Animal models | Adult male Sprague-Dawley rats |
Preparation Method | Rats were implanted with a radiotelemetry transmitter for core body temperature (Tc) monitoring and a guide cannula in the right lateral ventricle for intracerebroventricular (icv) injection. On the experiment day, rats received an intraperitoneal (i.p.) injection of bacterial endotoxin lipopolysaccharide (LPS; 30µg/kg) to induce fever, followed 30 minutes later by the icv injection of HS014 TFA or vehicle (artificial cerebrospinal fluid, aCSF). Tc and motor activity were recorded continuously, and tail skin temperature (Tsk) was measured hourly. |
Dosage form | 1µg in 5µl; icv; single injection. |
Applications | HS014 TFA had no significant effect on the LPS-induced febrile increase in core body temperature (Tc) or the associated decrease in tail skin temperature (Tsk) in rats. HS014 TFA also had no significant effect on Tc, Tsk, or motor activity in afebrile (saline-treated) rats. However, the same dose of HS014 TFA completely blocked the antipyretic and anti-vasoconstrictive effects of a co-administered selective MC4R agonist (MRLOB-0001; 150ng; icv) during the first phase of fever. |
References: | |
| Cas No. | SDF | ||
| Formula | C73H95F3N20O19S2 | M.Wt | 1677.78 |
| Solubility | DMSO : 100 mg/mL (59.60 mM; Need ultrasonic) | Storage | -20°C, away from moisture |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 596 μL | 2.9801 mL | 5.9603 mL |
| 5 mM | 119.2 μL | 596 μL | 1.1921 mL |
| 10 mM | 59.6 μL | 298 μL | 596 μL |
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Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 10 reference(s) in Google Scholar.)