title: Hypocretin (orexin) receptor 2
text: # Hypocretin (orexin) receptor 2
  
  Orexin receptor type 2 (Ox2R or $OX_2),$ also known as hypocretin receptor type 2 (HcrtR2), is a protein that in humans is encoded by the HCRTR2 gene.
  
  ## 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
  
  $OX_2$ is a G-protein coupled receptor expressed exclusively in the brain. It has 64% identity with $OX_1.$ $OX_2$ binds both orexin A and orexin B neuropeptides. $OX_2$ is involved in the central feedback mechanism that regulates feeding behaviour. Mice with enhanced $OX_2$ 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.
  
  ## Ligands
  
  ### Agonists
  
  * Danavorexton (TAK-925) – selective $OX_2$ receptor agonist
  * Firazorexton – selective $OX_2$ receptor agonist
  * Orexins – dual $OX_1$ and $OX_2$ receptor agonists
     * Orexin-A – approximately equipotent at the $OX_1$ and $OX_2$ receptors
     * Orexin-B – approximately 5- to 10-fold selectivity for the $OX_2$ receptor over the $OX_1$ receptor
  * SB-668875 – selective $OX_2$ receptor agonist
  * Suntinorexton – selective $OX_2$ receptor agonist
  * TAK-861 – selective $OX_2$ receptor agonist
  * TAK-994 – selective $OX_2$ receptor agonist
  
  ### Antagonists
  
  * Almorexant - Dual $OX_1$ and $OX_2$ antagonist
  * Daridorexant (nemorexant) - Dual $OX_1$ and $OX_2$ antagonist
  * EMPA - Selective $OX_2$ antagonist
  * Filorexant - Dual $OX_1$ and $OX_2$ antagonist
  * JNJ-10397049 (600x selective for $OX_2$ over $OX_1)$
  * Lemborexant - Dual $OX_1$ and $OX_2$ antagonist
  * MK-1064 - Selective $OX_2$ antagonist
  * MK-8133 - Selective $OX_2$ antagonist
  * SB-649,868 - Dual $OX_1$ and $OX_2$ antagonist
  * Seltorexant - Selective $OX_2$ antagonist
  * Suvorexant - Dual $OX_1$ and $OX_2$ antagonist
  * TCS-OX2-29 - Selective $OX_2$ antagonist
  * (3,4-dimethoxyphenoxy)alkylamino acetamides
  * Compound 1m - Selective $OX_2$ antagonist
  