| 词条 | Orexin receptor |
| 释义 |
| Name = hypocretin (orexin) receptor 1 | caption = | image = | width = | HGNCid = 4848 | Symbol = HCRTR1 | AltSymbols = | EntrezGene = 3061 | OMIM = 602392 | RefSeq = NM_001525 | UniProt = O43613 | PDB = | ECnumber = | Chromosome = 1 | Arm = p | Band = 33 | LocusSupplementaryData = }}{{infobox protein | Name = hypocretin (orexin) receptor 2 | caption = | image = | width = | HGNCid = 4849 | Symbol = HCRTR2 | AltSymbols = | EntrezGene = 3062 | OMIM = 602393 | RefSeq = NM_001526 | UniProt = O43614 | PDB = | ECnumber = | Chromosome = 6| Arm = p | Band = 11 | LocusSupplementaryData = -q11 }}{{Infobox protein family | Symbol = Orexin_rec2 | Name = Orexin receptor type 2 | image = | width = | caption = | Pfam = PF03827 | Pfam_clan = | InterPro = IPR004060 | SMART = | PROSITE = | MEROPS = | SCOP = | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }} The orexin receptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor that binds the neuropeptide orexin. There are two variants, OX1 and OX2, each encoded by a different gene ({{gene|HCRTR1}}, {{gene|HCRTR2}}).[1] Both orexin receptors exhibit a similar pharmacology - the 2 orexin peptides, orexin-A and orexin-B, bind to both receptors and, in each case, agonist binding results in an increase in intracellular calcium levels. However, orexin-B shows a 10-fold selectivity for orexin receptor type 2, whilst orexin-A is equipotent at both receptors.[2] Several orexin receptor antagonists are in development for potential use in sleep disorders.[3] Synthetic ligandsSeveral drugs[4] acting on the orexin system are under development, either orexin agonists for the treatment of conditions such as narcolepsy, or orexin antagonists for insomnia. No neuropeptide agonists are yet available, although synthetic Orexin-A polypeptide has been made available as a nasal spray and tested on monkeys. One non-peptide antagonist is currently available in the U.S., Merck's suvorexant (Belsomra),;[5] two additional agents are in development: SB-649,868 by GlaxoSmithKline, for sleep disorders, and ACT-462206, currently in human clinical trials.[6] Another drug in development, almorexant (ACT-078573) by Actelion, was abandoned due to adverse effects. Most ligands acting on the orexin system so far are polypeptides modified from the endogenous agonists Orexin-A and Orexin-B, however there are some subtype-selective non-peptide antagonists available for research purposes.
References1. ^{{cite journal |vauthors=Spinazzi R, Andreis PG, Rossi GP, Nussdorfer GG | title = Orexins in the regulation of the hypothalamic-pituitary-adrenal axis | journal = Pharmacol. Rev. | volume = 58 | issue = 1 | pages = 46–57 | year = 2006 | pmid = 16507882 | doi = 10.1124/pr.58.1.4 }} 2. ^{{cite journal |vauthors=Smart D, Jerman JC, Brough SJ, Rushton SL, Murdock PR, Jewitt F, Elshourbagy NA, Ellis CE, Middlemiss DN, Brown F | title = Characterization of recombinant human orexin receptor pharmacology in a Chinese hamster ovary cell-line using FLIPR | journal = Br. J. Pharmacol. | volume = 128 | issue = 1 | pages = 1–3 |date=September 1999 | pmid = 10498827 | pmc = 1571615 | doi = 10.1038/sj.bjp.0702780 | url = }} 3. ^{{cite journal |vauthors=Yin J, Mobarec JC, Kolb P, Rosenbaum DM | title = Crystal Structure of the Human Ox2 Orexin Receptor Bound to the Insomnia Drug Suvorexant | journal = Nature | volume = 519| issue = | pages = 247–250|date=December 2014 | pmid = 25533960| pmc = | doi = 10.1038/nature14035 | url = }} 4. ^{{cite journal |vauthors=Heifetz A, Morris GB, Biggin PC, Barker O, Fryatt T, Bentley J, Hallett D, Manikowski DP, Pal S, Reifegerste R, Slack M, Law R |title=Study of Human Orexin-1 and -2 G-Protein-Coupled Receptors with Novel and Published Antagonists by Modeling, Molecular Dynamics Simulations, and Site-Directed Mutagenesis | journal = Biochemistry | year=2012 | volume = 51 | issue = 15 | pages = 3178–3197 | doi = 10.1021/bi300136h | pmid=22448975}} 5. ^{{cite journal |vauthors=Baxter CA, Cleator ED, Karel MJ, Edwards JS, Reamer RA, Sheen FJ, Stewart GW, Strotman NA, Wallace DJ | title = The First Large-Scale Synthesis of MK-4305: A Dual Orexin Receptor Antagonist for the Treatment of Sleep Disorder | journal = Organic Process Research & Development | year = 2011 | volume = 15 | issue = 2 | pages = 367–375 | doi = 10.1021/op1002853}} 6. ^{{Cite journal|url = |title = Entry-into-humans study with ACT-462206, a novel dual orexin receptor antagonist, comparing its pharmacodynamics with almorexant|date = Sep 2014|journal = J Clin Pharmacol|accessdate = |doi = 10.1002/jcph.297|pmid = 24691844 |volume=54 |pages=979–86 |vauthors=Hoch M, van Gorsel H, van Gerven J, Dingemanse J}} External links
3 : Protein families|G protein-coupled receptors|Orexin antagonists |
| 随便看 |
|
开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。