Senktide

Tachykinin NK3 agonist CAS# 106128-89-6

Senktide

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Chemical structure

Senktide

3D structure

Chemical Properties of Senktide

Cas No. 106128-89-6 SDF Download SDF
PubChem ID 108147 Appearance Powder
Formula C40H55N7O11S M.Wt 841.97
Type of Compound N/A Storage Desiccate at -20°C
Solubility DMSO : 50 mg/mL (59.38 mM; Need ultrasonic)
Sequence DFFGLM

(Modifications: Asp-1 = Succinyl-Asp, Phe-3 = Me-Phe, Met-6 = C-terminal amide)

Chemical Name (3S)-4-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(3-carboxypropanoylamino)-4-oxobutanoic acid
SMILES CC(C)CC(C(=O)NC(CCSC)C(=O)N)NC(=O)CNC(=O)C(CC1=CC=CC=C1)N(C)C(=O)C(CC2=CC=CC=C2)NC(=O)C(CC(=O)O)NC(=O)CCC(=O)O
Standard InChIKey HMHYXLVEFVGOPM-QKUYTOGTSA-N
Standard InChI InChI=1S/C40H55N7O11S/c1-24(2)19-28(37(55)45-27(36(41)54)17-18-59-4)44-33(49)23-42-39(57)31(21-26-13-9-6-10-14-26)47(3)40(58)30(20-25-11-7-5-8-12-25)46-38(56)29(22-35(52)53)43-32(48)15-16-34(50)51/h5-14,24,27-31H,15-23H2,1-4H3,(H2,41,54)(H,42,57)(H,43,48)(H,44,49)(H,45,55)(H,46,56)(H,50,51)(H,52,53)/t27-,28-,29-,30-,31-/m0/s1
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of Senktide

DescriptionNK3 tachykinin receptor agonist. Causes direct excitation of dopamine neurons; enhances dopaminergic function. Induces locomotor activity.

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References on Senktide

The neurokinin-3 receptor agonist senktide facilitates the integration of memories for object, place and temporal order into episodic memory.[Pubmed:24972016]

Neurobiol Learn Mem. 2014 Oct;114:178-85.

Senktide, a potent neurokinin-3 receptor (NK3-R) agonist, has been shown to have promnestic effects in adult and aged rodents and to facilitate episodic-like memory (ELM) in mice when administrated before the learning trial. In the present study we assessed the effects of Senktide on memory consolidation by administering it post-trial (after the learning trial) in adult rats. We applied an ELM test, based on the integrated memory for object, place and temporal order, which we developed (Kart-Teke, de Souza Silva, Huston, & Dere, 2006). This test involves two learning trials and one test trial. We examined intervals of 1h and 23 h between the learning and test trials (experiment 1) in untreated animals and found that they exhibited intact ELM after a delay of 1 h, but not 23 h. In another test for ELM performed 7 days later, vehicle or Senktide (0.2 mg/kg, s.c.) was applied immediately after the second learning trial and the test was conducted 23 h later (experiment 2). Senktide treatment recovered components of ELM (memory for place and object) compared with vehicle-treated animals. After one more week, vehicle or Senktide (0.2 mg/kg, s.c.) was applied post-trial and the test conducted 6h later (experiment 3). The Senktide-treated group exhibited intact ELM, unlike the vehicle-treated group. Finally, animals received post-trial treatment with either vehicle or SR142801, a selective NK3-R antagonist (6 mg/kg, i.p.), 1 min before Senktide injection (0.2 mg/kg, s.c.) in the ELM paradigm and were tested 6h later (experiment 4). The vehicle+Senktide group showed intact ELM, while the SR142801+Senktide group did not. The results indicate that Senktide facilitated the consolidation or the expression of ELM and that the Senktide effect was NK3-R dependent.

Ovarian and hormonal responses to single or continuous peripheral administration of senktide, a neurokinin 3 receptor agonist, during the follicular phase in goats.[Pubmed:26295982]

Domest Anim Endocrinol. 2015 Oct;53:136-43.

The present study aimed to investigate the effects of single or continuous administration of a neurokinin 3 receptor agonist, Senktide, on hormonal and follicular dynamics in follicular phase goats. Goats were injected with PGF2alpha in the luteal phase and treated with an intravaginal progesterone device for 10 d. At 12 h after the cessation of progesterone treatment, the goats received a single intravenous injection of Senktide (200 nmol, n = 4) or vehicle (n = 4), or continuous intravenous infusion of Senktide (20 nmol/min, n = 6) or vehicle (n = 6) for 6 h. Blood sampling and ovarian ultrasonography were performed during the experiment. A single injection of Senktide did not influence the number of luteinizing hormone (LH) pulses and mean LH concentration. On the other hand, continuous injection of Senktide caused a sustained increase in LH secretion, and mean LH concentration in samples collected at 10-min intervals for 6 h after the start of infusion was higher than that of vehicle-treated goats (2.8 +/- 1.3 vs 1.0 +/- 0.6 ng/mL, P < 0.01). In 4 of 6 goats, LH concentrations reached their peaks during the 6-h Senktide infusion, and ovulation was observed at 48 h after the start of infusion without estrous behavior. The remaining 2 Senktide-treated goats and all vehicle-treated goats showed estrus and ovulated at 72 or 96 h after treatment. These results suggest that continuous infusion of Senktide in follicular phase goats can cause a sustained increase in LH and advance the time of ovulation.

Lactoferrin- and antitransferrin-modified liposomes for brain targeting of the NK3 receptor agonist senktide: preparation and in vivo evaluation.[Pubmed:25560308]

Int J Pharm. 2015 Feb 1;479(1):129-37.

The aim of this work was to evaluate the capability of lactoferrin- and antitransferrin-modified long circulating liposomes to deliver the hydrophilic peptide Senktide, a selective NK3 receptor agonist unable to cross the blood brain barrier, to central nervous system by using an indirect method based on in vivo microdialysis studies to estimate the responsiveness of nucleus accumbens shell dopamine to Senktide. To this purpose, Senktide was encapsulated in different targeted and not-targeted stealth liposomes prepared using film hydration method. Formulations were characterized in terms of morphology, size distribution, zeta potential, encapsulation efficiency, and antibody presence on the liposome surface. In vivo microdialysis studies were performed injecting intravenously the Senktide-loaded liposomes and comparing obtained dopamine levels with those found with the free Senktide given intracerebroventricularly. Results showed that all vesicles were spherical, small in size (around 120 nm), homogeneously dispersed, and slightly negatively charged. TEM analysis, using an anti IgG secondary antibody with 10nm gold nanoparticles at its distal end, demonstrated the successful linkage of the antibody on the liposomal surface. Intravenously administered in rats, Senktide-loaded targeted stealth liposomes elicited a significant increase of dialysate dopamine in the nucleus accumbens shell, which was comparable to that of the free Senktide given intracerebroventricularly when antitransferrin-targeted liposomes were tested. On the contrary, control stealth liposomes did not affect dopamine levels. Senktide brain levels were higher using the antitransferrin-targeted liposomes in comparison with the lactoferrin ones, while the opposite was obtained in the liver tissue where the highest Senktide accumulation was always found.

Effects of senktide, a neurokinin 3 receptor agonist, on luteinizing hormone secretion and follicular development in anestrous Shiba goats: a pilot study.[Pubmed:25362998]

BMC Res Notes. 2014 Nov 3;7:773.

BACKGROUND: Recent studies suggest that neurokinin B and its receptor, neurokinin 3 receptor, have an essential role in the regulation of gonadotropin-releasing hormone and luteinizing hormone (LH) release in several mammalian species. As the first trial, this pilot study reports the effect of intravenous treatment with Senktide, a selective agonist of neurokinin 3 receptor, on LH secretion, follicular development in female goats that were clinically diagnosed with anestrus. FINDINGS: Anestrous goats were intravenously administered 200 nmol Senktide at 4-h intervals for 24 h. Most of them examined (5/6 cases) showed a pulsatile increase in LH secretion after each injection of Senktide, whereas the remaining one case showed a surge-like increase of LH secretion. Ovulation was confirmed in 5/6 cases at the range of 48-96 h after the beginning of treatment. CONCLUSIONS: This pilot study demonstrated that intravenous treatment with Senktide has therapeutic action in goats with anestrus by inducing LH release, which could promote follicular development and ovulation.

The tachykinin NK3 receptor agonist senktide induces locomotor activity in male Mongolian gerbils.[Pubmed:18930726]

Eur J Pharmacol. 2008 Dec 14;600(1-3):87-92.

The tachykinin family of receptors has been of strong interest recently due to the potential of the tachykinin NK(3) receptor antagonism in treatment of schizophrenia. However, critical differences in the tachykinin NK(3) receptor between rats, mice and humans make rats and mice less acceptable species for testing tachykinin NK(3) receptor antagonism. This has led to testing of tachykinin NK(3) receptor activity in gerbils and guinea pigs. As these species are much less common laboratory animals than rats and mice, there is a relative paucity of in vivo testing models for tachykinin NK(3) receptor activation. In the present study, locomotor activity induced by the tachykinin NK(3) receptor agonist Senktide was characterized. Injection of Senktide i.c.v. was found to dose-dependently induce hyperlocomotion from a dose of 0.06 nmol to the maximal dose tested, 0.6 nmol. Locomotion induced by 0.1 nmol of Senktide could be blocked by injection of the tachykinin NK(3) receptor antagonists SB222200 (10 and 30 mg/kg i.p.) and talnetant (SB223412; 10 and 30 mg/kg i.p.), as well as by osanetant (SR142801; 10 and 30 mg/kg i.p.) when administered in a vehicle containing vitamin E and glycofurol. Senktide-induced activity was also reversed by the antipsychotics haloperidol (0.3 and 1 mg/kg p.o.) and risperidone (1 mg/kg p.o.), but not by the serotonin 5HT(2a/c) receptor antagonist MDL100907 (tested at 0.1, 0.3 and 1 mg/kg p.o.). Hyperlocomotion induced by 0.03 nmol of Senktide was potentiated by antagonism of the tachykinin NK(1) receptor with aprepitant (1, 3 and 10 mg/kg, p.o.). Thus, hyperlocomotion induced by Senktide in gerbils is a tachykinin NK(3) receptor-mediated behavior that is appropriate for use in testing tachykinin NK(3) receptor activity of novel compounds.

The selective NK3 receptor agonist senktide excites a subpopulation of dopamine-sensitive neurones in the rat substantia nigra pars compacta in vitro.[Pubmed:1375857]

Br J Pharmacol. 1992 Jan;105(1):3-5.

Intra- and extracellular recordings were made from substantia nigra zona compacta neurones from an in vitro rat brain slice preparation. A subpopulation of dopamine-sensitive neurones were encountered which were potently excited by bath application of the NK3 receptor agonist, Senktide. On these Senktide-sensitive neurones, NK1 and NK2 receptor agonists were inactive. The excitatory action of Senktide supports a role for tachykinins as putative neurotransmitters in the basal ganglia.

Characterization of NK-3 binding sites in rat and guinea pig cortical membranes by the selective ligand [3H]Senktide.[Pubmed:1712430]

Neuropeptides. 1991 Mar;18(3):107-14.

We have used [3H]Senktide, a selective Neurokinin B receptor ligand, for the characterization of NK-3 receptors in rat and guinea pig CNS membranes. Scatchard analysis of saturation binding studies in cerebral cortex membranes indicated that this ligand bound to a single site with apparent high affinity (KD = 4.6 +/- 1.6 and 3.1 +/- 0.37 nM, Bmax = 13.7 +/- 1.6 and 21.8 +/- 2.2 fmol/mg protein in rat and guinea pig membranes, respectively). However, in competition studies with a group of neurokinins and related peptides two different rank orders of affinities were obtained, as follows: NKB greater than [MePhe7]-NKB greater than or equal to Arg0-NKB greater than or equal to Senktide much greater than NKA greater than SP, in rat membranes, and [MePhe7]NKB greater than Senktide = NKB greater than Arg0-NKB much greater than SP greater than NKA, in guinea pig membranes.

Description

Senktide is a tachykinin NK3 receptor agonist.

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