Английская Википедия:Hypocretin (orexin) receptor 2
Шаблон:Short description Шаблон:Infobox gene Шаблон:Infobox protein family Orexin receptor type 2 (Ox2R or OX2), also known as hypocretin receptor type 2 (HcrtR2), is a protein that in humans is encoded by the HCRTR2 gene.[1]
Structure
The structure of the receptor has been solved to 2.5 Å resolution as a fusion protein bound to suvorexant using lipid-mediated crystallization.[2]
Function
OX2 is a G-protein coupled receptor expressed exclusively in the brain. It has 64% identity with OX1. OX2 binds both orexin A and orexin B neuropeptides. OX2 is involved in the central feedback mechanism that regulates feeding behaviour.[1] Mice with enhanced OX2 signaling are resistant to high-fat diet-induced obesity.[3]
This receptor is activated by Hipocretin, which is a wake-promoting hypothalamic neuropeptide that acts as a critical regulator of sleep in animals as Zebrafish or Mammals. This protein has mutations in Astyanax mexicanus that reduces the sleep needs of the cavefish. [4]
Ligands
Agonists
- Danavorexton (TAK-925) – selective OX2 receptor agonist
- Firazorexton – selective OX2 receptor agonist[5][6]
- Orexins – dual OX1 and OX2 receptor agonists
- SB-668875 – selective OX2 receptor agonist
- Suntinorexton – selective OX2 receptor agonist[5][6]
- TAK-861 – selective OX2 receptor agonist[9]
Antagonists
- Almorexant - Dual OX1 and OX2 antagonist
- Daridorexant (nemorexant) - Dual OX1 and OX2 antagonist
- EMPA - Selective OX2 antagonist
- Filorexant - Dual OX1 and OX2 antagonist
- JNJ-10397049 (600x selective for OX2 over OX1)[10]
- Lemborexant - Dual OX1 and OX2 antagonist
- MK-1064 - Selective OX2 antagonist[11]
- MK-8133 - Selective OX2 antagonist[12]
- SB-649,868 - Dual OX1 and OX2 antagonist
- Seltorexant - Selective OX2 antagonist
- Suvorexant - Dual OX1 and OX2 antagonist
- TCS-OX2-29 - Selective OX2 antagonist
- (3,4-dimethoxyphenoxy)alkylamino acetamides[13]
- Compound 1m - Selective OX2 antagonist[14]
See also
References
Further reading
- Шаблон:Cite journal
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Шаблон:NLM content Шаблон:G protein-coupled receptors Шаблон:Orexin receptor modulators
- ↑ 1,0 1,1 Шаблон:Cite web
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- ↑ 5,0 5,1 Шаблон:Cite web
- ↑ 6,0 6,1 Шаблон:Cite patent
- ↑ 7,0 7,1 Шаблон:Cite journal
- ↑ 8,0 8,1 Шаблон:Cite journal
- ↑ Шаблон:Cite web
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