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Revision as of 01:30, 31 July 2010 editCitation bot 1 (talk | contribs)Bots130,044 editsm Citations: Tweaked: doi. You can use this bot yourself! Report bugs here.← Previous edit		Latest revision as of 22:00, 10 October 2024 edit undoDMacks (talk | contribs)Edit filter managers, Autopatrolled, Administrators186,468 editsm DMacks moved page PK-11195 to PK 11195: Misspelled: ...but for visible things, page-name must match text and the refs do verify the space-not-hyphen
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	{{chembox		{{chembox
			| Verifiedfields = changed
	| ImageFile = PK-11195_structure.png
			| Watchedfields = changed
	| ImageSize = 200px
			| verifiedrevid = 376354879
⚫	| IUPACName = N-butan-2-yl-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide
	| OtherNames = PK-11195		| ImageFile = PK-11195.svg
		⚫	| IUPACName = ''N''-Butan-2-yl-1-(2-chlorophenyl)-''N''-methylisoquinoline-3-carboxamide
			| OtherNames = PK 11195
	| Section1 = {{Chembox Identifiers		| Section1 = {{Chembox Identifiers
	| CASNo = 85340-56-3		| CASNo = 85532-75-8
	| CASNo_Ref = {{cascite}}		| CASNo_Ref = {{cascite|correct|CAS}}
	| PubChem = 1345		| PubChem = 1345
			| UNII_Ref = {{fdacite|correct|FDA}}
⚫	| SMILES = CCC(C)N(C)C(=O)c3cc1ccccc1c(n3)-c2ccccc2Cl
			| UNII = YNF83VN1RL
⚫	}}
			| ChEBI_Ref = {{ebicite|changed|EBI}}
			| ChEBI = 73290
			| ChEMBL_Ref = {{ebicite|changed|EBI}}
			| ChEMBL = 15313
			| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
			| ChemSpiderID = 1305
		⚫	| SMILES = CCC(C)N(C)C(=O)c3cc1ccccc1c(n3)-c2ccccc2Cl
			| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
			| StdInChI = 1S/C21H21ClN2O/c1-4-14(2)24(3)21(25)19-13-15-9-5-6-10-16(15)20(23-19)17-11-7-8-12-18(17)22/h5-14H,4H2,1-3H3
			| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
			| StdInChIKey = RAVIZVQZGXBOQO-UHFFFAOYSA-N
		⚫	}}
	| Section2 = {{Chembox Properties		| Section2 = {{Chembox Properties
	| Formula = C<sub>21</sub>H<sub>21</sub>ClN<sub>2</sub>O		| Formula = C<sub>21</sub>H<sub>21</sub>ClN<sub>2</sub>O
	| MolarMass = 352.856 g/mol		| MolarMass = 352.856 g/mol
	}}		}}
	| Section3 = {{Chembox Hazards		| Section3 = {{Chembox Hazards
	| MainHazards =		| MainHazards =
⚫	}}
	}}		}}
		⚫	}}
		⚫	'''PK 11195''' is an isoquinoline carboxamide which binds selectively to the ] (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,<ref name="pmid8389223">{{cite journal |vauthors=Pike VW, Halldin C, Crouzel C, Barré L, Nutt DJ, Osman S, Shah F, Turton DR, Waters SL |title=Radioligands for PET studies of central benzodiazepine receptors and PK (peripheral benzodiazepine) binding sites--current status |journal=Nuclear Medicine and Biology |volume=20 |issue=4 |pages=503–25 |date=May 1993 |pmid=8389223 |doi= 10.1016/0969-8051(93)90082-6}}</ref> although it is starting to be replaced by newer and more selective ligands.<ref name="pmid19075709">{{cite journal |vauthors=Doorduin J, de Vries EF, Dierckx RA, Klein HC |title=PET imaging of the peripheral benzodiazepine receptor: monitoring disease progression and therapy response in neurodegenerative disorders |journal=Current Pharmaceutical Design |volume=14 |issue=31 |pages=3297–315 |year=2008 |pmid=19075709 |doi= 10.2174/138161208786549443}}</ref>
		⚫	Early autoradiographic studies using tritiated PK 11195 (PK 11195) demonstrated that in the central nervous system (CNS) of rodents, it binds primarily to the ependymal walls, choroid plexus, and olfactory bulb. However, there is a robust and widespread increase in PK 11195 binding in the injured nervous system. The binding sites have since been determined to be on glial cells, including microglia, astrocytes, and infiltrating macrophages. The binding of PK 11195 is considered to be a useful tool in the assessment of neuronal damage.<ref name="pmid12468021">{{cite journal |vauthors=Cagnin A, Gerhard A, Banati RB |title=In vivo imaging of neuroinflammation |journal=European Neuropsychopharmacology |volume=12 |issue=6 |pages=581–6 |date=December 2002 |pmid=12468021 |doi= 10.1016/s0924-977x(02)00107-4|s2cid=35085112 }}</ref><ref name="pmid12558962">{{cite journal |vauthors=Weissman BA, Raveh L |title=Peripheral benzodiazepine receptors: on mice and human brain imaging |journal=Journal of Neurochemistry |volume=84 |issue=3 |pages=432–7 |date=February 2003 |pmid=12558962 |doi= 10.1046/j.1471-4159.2003.01568.x|s2cid=38106157 |doi-access=free }}</ref>
⚫	'''PK-11195''' is an isoquinoline carboxamide which binds selectively to the ] (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,<ref name="pmid8389223">{{cite journal |author=Pike VW, Halldin C, Crouzel C, Barré L, Nutt DJ, Osman S, Shah F, Turton DR, Waters SL |title=Radioligands for PET studies of central benzodiazepine receptors and PK (peripheral benzodiazepine) binding sites--current status |journal=Nuclear Medicine and Biology |volume=20 |issue=4 |pages=503–25 |year=1993 |month=May |pmid=8389223 |doi= 10.1016/0969-8051(93)90082-6|url=}}</ref> although it is starting to be replaced by newer and more selective ligands.<ref name="pmid19075709">{{cite journal |author=Doorduin J, de Vries EF, Dierckx RA, Klein HC |title=PET imaging of the peripheral benzodiazepine receptor: monitoring disease progression and therapy response in neurodegenerative disorders |journal=Current Pharmaceutical Design |volume=14 |issue=31 |pages=3297–315 |year=2008 |pmid=19075709 |doi= 10.2174/138161208786549443|url=}}</ref>
		⚫	In addition to being a marker of neuronal damage in animal models of CNS damage, PK 11195 has been used successfully with human brain imaging techniques. (''R'')-PK 11195 has been used in positron emission tomography (PET) scanning to visualize brain inflammation in patients with neuronal damage. Increases in (''R'')-PK 11195 binding have been reported in patients with stroke, ]<ref name="pmid21764792">{{cite journal |vauthors=Folkersma H, Boellaard R, Yaqub M, Kloet RW, Windhorst AD, Lammertsma AA, Vandertop WP, van Berckel BN |title=Widespread and prolonged increase in (R)-(11)C-PK 11195 binding after traumatic brain injury |journal=J Nucl Med |volume=52 |issue=8 |pages=1235–9 |year=2011 |pmid=21764792 |doi= 10.2967/JNUMED.110.084061|doi-access=free }}</ref> and in patients with chronic neurodegenerative conditions including ] and ].<ref name="pmid17352938">{{cite journal |vauthors=Tai YF, Pavese N, Gerhard A, Tabrizi SJ, Barker RA, Brooks DJ, Piccini P |title=Imaging microglial activation in Huntington's disease |journal=Brain Research Bulletin |volume=72 |issue=2–3 |pages=148–51 |date=April 2007 |pmid=17352938 |doi=10.1016/j.brainresbull.2006.10.029 |s2cid=6395304 }}</ref><ref name="pmid17592621">{{cite journal |vauthors=Bartels AL, Leenders KL |title=Neuroinflammation in the pathophysiology of Parkinson's disease: evidence from animal models to human in vivo studies with PK 11195 PET |journal=Movement Disorders |volume=22 |issue=13 |pages=1852–6 |date=October 2007 |pmid=17592621 |doi=10.1002/mds.21552 }}</ref>
⚫	Early autoradiographic studies using tritiated PK-11195 (-PK11195) demonstrated that in the central nervous system (CNS) of rodent, 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 -PK11195 binding. The binding sites have since been determined to be on glial cells, including microglia, astrocytes, and infiltrating macrophages. The binding of -PK11195 is considered to be a useful tool in the assessment of neuronal damage.<ref name="pmid12468021">{{cite journal |author=Cagnin A, Gerhard A, Banati RB |title=In vivo imaging of neuroinflammation |journal=European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology |volume=12 |issue=6 |pages=581–6 |year=2002 |month=December |pmid=12468021 |doi= |url=}}</ref><ref name="pmid12558962">{{cite journal |author=Weissman BA, Raveh L |title=Peripheral benzodiazepine receptors: on mice and human brain imaging |journal=Journal of Neurochemistry |volume=84 |issue=3 |pages=432–7 |year=2003 |month=February |pmid=12558962 |doi= 10.1046/j.1471-4159.2003.01568.x|url=}}</ref>
			The first high-resolution 3D solution structure of mammalian (mouse) translocator protein (TSPO) in a complex with its diagnostic PK 11195 ligand was determined by using NMR spectroscopy techniques by scientists from the Max-Planck Institute for Biophysical Chemistry in Goettingen in Germany in March 2014<ref>L. Jaremko, M. Jaremko, K. Giller, S. Becker, M. Zweckstetter, Structure of the mitochondrial translocator protein in complex with a diagnostic ligand, Science, 343 (2014) 1363-1366</ref> 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 PK 11195 ligand forming a stable hydrophobic binding pocket that can also be regarded as the complex's hydrophobic core. The mammalian TSPO in a complex with diagnostic ligand is monomeric.
⚫	In addition to being a marker of neuronal damage in animal models of CNS damage, PK-11195 has been used successfully with human brain imaging techniques. (R)-PK11195 has been used in positron emission tomography (PET) scanning to visualize brain inflammation in patients with neuronal damage. Increases in (R)-PK11195 binding have been reported in patients with stroke, traumatic brain injury and in patients with chronic neurodegenerative conditions including ] and ].<ref name="pmid17352938">{{cite journal |author=Tai YF, Pavese N, Gerhard A, Tabrizi SJ, Barker RA, Brooks DJ, Piccini P |title=Imaging microglial activation in Huntington's disease |journal=Brain Research Bulletin |volume=72 |issue=2-3 |pages=148–51 |year=2007 |month=April |pmid=17352938 |doi=10.1016/j.brainresbull.2006.10.029 |url=}}</ref><ref name="pmid17592621">{{cite journal |author=Bartels AL, Leenders KL |title=Neuroinflammation in the pathophysiology of Parkinson's disease: evidence from animal models to human in vivo studies with -PK11195 PET |journal=Movement Disorders : Official Journal of the Movement Disorder Society |volume=22 |issue=13 |pages=1852–6 |year=2007 |month=October |pmid=17592621 |doi=10.1002/mds.21552 |url=}}</ref>
			The loop located in between TM1 and TM2 helices closes the entrance to the space between helices in which are bound with PK 11195 molecule. Site-directed mutagenesis studies of mTSPO revealed that region important for PK 11195 binding comprise amino acids from 41 to 51, because the deletion of this region resulted in the decrease in PK 11195 binding.<ref>J. Fan, P. Lindemann, M.G. Feuilloley, V. Papadopoulos, Structural and functional evolution of the translocator protein (18 kDa), Curr Mol Med, 12 (2012) 369-386</ref>
	{{pharm-stub}}
	==References==		==References==
	{{reflist}}		{{Reflist}}
			{{Translocator protein modulators}}
			{{Xenobiotic-sensing receptor modulators}}
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