Hypocretin (orexin) receptor 2

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. It should not be confused for the protein CD200R1 which shares the alias OX2R but is a distinct, unrelated gene located on the human chromosome 3.

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.

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. Mice with enhanced OX2 signaling are resistant to high-fat diet-induced obesity.

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.

Agonists

 * Danavorexton (TAK-925) – selective OX2 receptor agonist
 * Firazorexton – selective OX2 receptor agonist
 * Orexins – dual OX1 and OX2 receptor agonists
 * Orexin-A – approximately equipotent at the OX1 and OX2 receptors
 * Orexin-B – approximately 5- to 10-fold selectivity for the OX2 receptor over the OX1 receptor
 * SB-668875 – selective OX2 receptor agonist
 * Suntinorexton – selective OX2 receptor agonist
 * TAK-861 – selective OX2 receptor agonist

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)
 * Lemborexant - Dual OX1 and OX2 antagonist
 * MK-1064 - Selective OX2 antagonist
 * MK-8133 - Selective OX2 antagonist
 * 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
 * Compound 1m - Selective OX2 antagonist