PK-11195 (original) (raw)
PK-11195 is an isoquinoline carboxamide which binds selectively to the peripheral benzodiazepine receptor (PBR) (also known as the mitochondrial 18 kDa translocator protein or TSPO). It is one of the most commonly used PBR ligands due to its high affinity for the PBR in all species, although it is starting to be replaced by newer and more selective ligands.
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| dbo:abstract | PK-11195 is an isoquinoline carboxamide which binds selectively to the peripheral benzodiazepine receptor (PBR) (also known as the mitochondrial 18 kDa translocator protein or TSPO). It is one of the most commonly used PBR ligands due to its high affinity for the PBR in all species, although it is starting to be replaced by newer and more selective ligands. Early autoradiographic studies using tritiated PK11195 ([3H]PK11195) demonstrated that in the central nervous system (CNS) of rodents, it binds primarily to the ependymal walls, choroid plexus, and olfactory bulb. However, in the injured nervous system there is a robust and widespread increase in [3H]PK11195 binding. The binding sites have since been determined to be on glial cells, including microglia, astrocytes, and infiltrating macrophages. The binding of [3H]PK11195 is considered to be a useful tool in the assessment of neuronal damage. In addition to being a marker of neuronal damage in animal models of CNS damage, PK11195 has been used successfully with human brain imaging techniques. (R)-[11C]PK11195 has been used in positron emission tomography (PET) scanning to visualize brain inflammation in patients with neuronal damage. Increases in (R)-[11C]PK11195 binding have been reported in patients with stroke, traumatic brain injury and in patients with chronic neurodegenerative conditions including Huntington's disease and Parkinson's disease. The first high-resolution 3D solution structure of mammalian (mouse) translocator protein (TSPO) in a complex with its diagnostic PK11195 ligand was determined by means of NMR spectroscopy techniques by scientists from the Max-Planck Institute for Biophysical Chemistry in Goettingen in Germany in March 2014 and has a PDB id: 2MGY. The complex stoichiometry was found to be 1 : 1 as the one consistent set of 1H ligand resonances was found with the NOE contacts to five transmembrane helices (TM) in the upper cytosolic part of the protein channel. Residues involved in the ligand binding having direct NOE contacts with the ligand were identified and are as follows A23, V26, L49, V26, A50, I52, W107, L114, A147, L150. These residues are wrapped around the PK11195 ligand forming a stable hydrophobic binding pocket that can be also regarded as the hydrophobic core of the complex. The mammalian TSPO in a complex with diagnostic ligand is monomeric. The loop located in between TM1 and TM2 helices closes the entrance to the space between helices in which are bound with PK11195 molecule. Site-directed mutagenesis studies of mTSPO revealed that region important for PK11195 binding comprise amino acids from 41 to 51, because the deletion of this region resulted in the decrease in PK11195 binding. (en) |
| dbo:alternativeName | PK-11195 (en) |
| dbo:iupacName | N-Butan-2-yl-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide (en) |
| dbo:thumbnail | wiki-commons:Special:FilePath/PK-11195.svg?width=300 |
| dbo:wikiPageID | 7180223 (xsd:integer) |
| dbo:wikiPageLength | 6956 (xsd:nonNegativeInteger) |
| dbo:wikiPageRevisionID | 1006201328 (xsd:integer) |
| dbo:wikiPageWikiLink | dbr:Huntington's_disease dbc:Enones dbr:Traumatic_brain_injury dbc:TSPO_ligands dbr:Parkinson's_disease dbc:Isoquinolines dbr:TSPO_(protein) |
| dbp:imagefile | PK-11195.svg (en) |
| dbp:iupacname | N-Butan-2-yl-1--N-methylisoquinoline-3-carboxamide (en) |
| dbp:othernames | PK-11195 (en) |
| dbp:verifiedfields | changed (en) |
| dbp:verifiedrevid | 376354879 (xsd:integer) |
| dbp:watchedfields | changed (en) |
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| dcterms:subject | dbc:Enones dbc:TSPO_ligands dbc:Isoquinolines |
| gold:hypernym | dbr:Carboxamide |
| rdf:type | owl:Thing dul:ChemicalObject dbo:ChemicalSubstance wikidata:Q11173 yago:Ligand115110307 yago:Matter100020827 yago:PhysicalEntity100001930 dbo:ChemicalCompound dbo:Drug yago:Substance100020090 yago:WikicatTSPOLigands umbel-rc:ChemicalSubstanceType |
| rdfs:comment | PK-11195 is an isoquinoline carboxamide which binds selectively to the peripheral benzodiazepine receptor (PBR) (also known as the mitochondrial 18 kDa translocator protein or TSPO). It is one of the most commonly used PBR ligands due to its high affinity for the PBR in all species, although it is starting to be replaced by newer and more selective ligands. (en) |
| rdfs:label | PK-11195 (en) |
| owl:sameAs | freebase:PK-11195 yago-res:PK-11195 wikidata:PK-11195 http://azb.dbpedia.org/resource/پیکی-۱۱۱۹۵ dbpedia-fa:PK-11195 dbpedia-sh:PK-11195 dbpedia-sr:PK-11195 https://global.dbpedia.org/id/4sqLm |
| prov:wasDerivedFrom | wikipedia-en:PK-11195?oldid=1006201328&ns=0 |
| foaf:depiction | wiki-commons:Special:FilePath/PK-11195.svg |
| foaf:isPrimaryTopicOf | wikipedia-en:PK-11195 |
| is dbo:wikiPageRedirects of | dbr:PK11195 |
| is dbo:wikiPageWikiLink of | dbr:Ritter_reaction dbr:Ro5-4864 dbr:PK11195 dbr:Translocator_protein |
| is foaf:primaryTopic of | wikipedia-en:PK-11195 |
