Synonym
GSK1059865; GSK 1059865; GSK-1059865
IUPAC/Chemical Name
((2S,5S)-2-(((5-bromopyridin-2-yl)amino)methyl)-5-methylpiperidin-1-yl)(3-fluoro-2-methoxyphenyl)methanone
InChi Key
TWCRHJLMMAYSTE-ZFWWWQNUSA-N
InChi Code
InChI=1S/C20H23BrFN3O2/c1-13-6-8-15(11-24-18-9-7-14(21)10-23-18)25(12-13)20(26)16-4-3-5-17(22)19(16)27-2/h3-5,7,9-10,13,15H,6,8,11-12H2,1-2H3,(H,23,24)/t13-,15-/m0/s1
SMILES Code
O=C(N1[C@H](CNC2=NC=C(Br)C=C2)CC[C@H](C)C1)C3=CC=CC(F)=C3OC
Appearance
To be determined
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 -4 C for short term (days to weeks) or -20 C for long term(months to years).
Solubility
To be determined
Shelf Life
>2 years if stored properly
Drug Formulation
To be determined
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
GSK1059865 specifically targets the orexin 1 receptor (OX1R), acting as a potent and selective antagonist. This compound was shown to reduce ethanol drinking behavior in ethanol-dependent mice, indicating its potential for modulating addiction-related behaviors through orexin signaling. The selectivity of GSK1059865 suggests that it might be useful in treating alcohol dependence without significantly affecting other reward-seeking behaviors.
In vitro activity:
In vitro, GSK1059865 is a potent, selective antagonist of the orexin 1 receptor (OX1R). It binds to the receptor with high affinity and inhibits orexin A-induced calcium mobilization, which is a key signaling pathway. This bioactivity supports its potential for modulating behaviors linked to addiction, particularly alcohol dependence.
In vivo activity:
In vivo, GSK1059865 significantly reduces ethanol consumption in ethanol-dependent mice in a dose-dependent manner. Notably, it does not affect the intake of non-alcoholic substances like sucrose, indicating its specificity in targeting alcohol-related behaviors. This suggests its potential as a treatment for alcohol dependence without interfering with general reward-seeking behaviors.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
436.33
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
1: Lopez MF, Moorman DE, Aston-Jones G, Becker HC. The highly selective
orexin/hypocretin 1 receptor antagonist GSK1059865 potently reduces ethanol
drinking in ethanol dependent mice. Brain Res. 2016 Apr 1;1636:74-80. doi:
10.1016/j.brainres.2016.01.049. Epub 2016 Feb 4. PMID: 26851547; PMCID:
PMC4808605.
2: Merlo Pich E, Melotto S. Orexin 1 receptor antagonists in compulsive behavior
and anxiety: possible therapeutic use. Front Neurosci. 2014 Feb 13;8:26. doi:
10.3389/fnins.2014.00026. PMID: 24592206; PMCID: PMC3923148.
3: Gozzi A, Turrini G, Piccoli L, Massagrande M, Amantini D, Antolini M,
Martinelli P, Cesari N, Montanari D, Tessari M, Corsi M, Bifone A. Functional
magnetic resonance imaging reveals different neural substrates for the effects
of orexin-1 and orexin-2 receptor antagonists. PLoS One. 2011 Jan
28;6(1):e16406. doi: 10.1371/journal.pone.0016406. PMID: 21307957; PMCID:
PMC3030585.
4: Piccoli L, Micioni Di Bonaventura MV, Cifani C, Costantini VJ, Massagrande M,
Montanari D, Martinelli P, Antolini M, Ciccocioppo R, Massi M, Merlo-Pich E, Di
Fabio R, Corsi M. Role of orexin-1 receptor mechanisms on compulsive food
consumption in a model of binge eating in female rats. Neuropsychopharmacology.
2012 Aug;37(9):1999-2011. doi: 10.1038/npp.2012.48. Epub 2012 May 9. PMID:
22569505; PMCID: PMC3398727.
5: Gozzi A, Lepore S, Vicentini E, Merlo-Pich E, Bifone A. Differential effect
of orexin-1 and CRF-1 antagonism on stress circuits: a fMRI study in the rat
with the pharmacological stressor Yohimbine. Neuropsychopharmacology. 2013
Oct;38(11):2120-30. doi: 10.1038/npp.2013.109. Epub 2013 May 8. PMID: 23736277;
PMCID: PMC3773661.