PK-11195 C-11, R-

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H21ClN2O
Molecular Weight	351.858
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC[C@@H](C)N([11CH3])C(=O)C1=NC(=C2C=CC=CC2=C1)C3=C(Cl)C=CC=C3

InChI

InChIKey=RAVIZVQZGXBOQO-NIQXDKTISA-N

InChI=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/t14-/m1/s1/i3-1

HIDE SMILES / InChI

Molecular Formula	C21H21ClN2O
Molecular Weight	351.858
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8389223 | https://clinicaltrials.gov/ct2/show/NCT00696371 | https://www.ncbi.nlm.nih.gov/pubmed/23715902 | https://www.ncbi.nlm.nih.gov/pubmed/24703991 | https://www.ncbi.nlm.nih.gov/pubmed/22524272

PK-11195 is a selective antagonist of the Translocator Protein (TSPO). The C11 radiolabeled isotope of PK-11195 ([11C]-(R)-PK-11195) has been used effectively for diagnostic PET imaging in a number of CNS conditions where imaging of TSPO is informative (the S- enantiomer is not used). Applicable conditions including Schizophrenia, Multiple Sclerosis, and Traumatic Brain Injuries where it has been particularly useful for detection of increased microglial activation. It has also been investigated as means to monitor the role of Toll-Like Receptor-4 (TLR-4) after cerebral ischemia in mice. It should be noted that the unlabeled PK-11195 had been investigated for a number of potential therapeutic uses but did not progress beyond animal and cell models.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Translocator protein 13 Target ID: P30536 Gene ID: 706.0 Gene Symbol: TSPO Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/22524272 \| https://www.ncbi.nlm.nih.gov/pubmed/6667063	Antagonist 2778
Toll-like receptor 4 6 Target ID: Q9QUK6 Gene ID: 21898.0 Gene Symbol: Tlr4 Target Organism: Mus musculus (Mouse) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26787106	Binding Agent 1064

Conditions

Condition	Modality	Highest Phase	Product
Schizophrenia 298 Sources: https://clinicaltrials.gov/ct2/show/NCT00205608	Diagnostic	Phase I 428	Unknown Approved Use Unknown
Multiple sclerosis 104 Sources: https://clinicaltrials.gov/ct2/show/NCT03134716	Diagnostic	Not Provided 504	Unknown Approved Use Unknown
Traumatic brain injury 9 Sources: https://clinicaltrials.gov/ct2/show/NCT00205582	Diagnostic	Phase I 428	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
517 MBq single, intravenous Dose: 517 MBq Route: intravenous Route: single Dose: 517 MBq Sources: https://pubmed.ncbi.nlm.nih.gov/23715902	unhealthy n = 23 Health Status: unhealthy Condition: Glioma Sex: M+F Food Status: UNKNOWN Population Size: 23 Sources: https://pubmed.ncbi.nlm.nih.gov/23715902	Sources: https://pubmed.ncbi.nlm.nih.gov/23715902

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 BCRP 699 CYP19A1 60	P-gp 1537 BCRP 561	rCYP2A1 1 rCYP2B1 1 rCYP2C11 1 rCYP2B2 1 rCYP3A1/2 1

Drug as perpetrator

Target	Modality	Activity
CYP19A1 60	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743083#sid=144210937	inconclusive [IC50 39.5373 uM]
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16051742/	yes
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16051742/	yes
rCYP2A1 1	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/10534307/	yes
rCYP2B1 1	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/2815828/ \| https://pubmed.ncbi.nlm.nih.gov/10534307/	yes
rCYP2B2 1	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/10534307/	yes
rCYP2C11 2	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/10534307/	yes
rCYP3A1/2 1	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/10534307/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21321274/	no
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21321274/	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/588834#sid=50104534

Sourcing

Vendor/Aggregator	ID	URL
ChEMBL	CHEMBL2206280
ChemIDplus	157727225	https://chem.nlm.nih.gov/chemidplus/id/0157727225
Wikidata	Q27279080

PubMed

Title	Date	PubMed
[¹¹C]-(R)PK11195 tracer kinetics in the brain of glioma patients and a comparison of two referencing approaches.	2013 Sep	23715902
The 18-kDa mitochondrial translocator protein in human gliomas: an 11C-(R)PK11195 PET imaging and neuropathology study.	2015 Apr	25722450

Patents

Sample Use Guides

In Vivo Use Guide

For PET imaging in glioma patients and healthy volunteers [11C]-(R)PK11195 was administered intravenously as a slow bolus over 15 seconds in a dose of 1.6 ± 0.8 micrograms and 2.4 ± 2.1 micrograms respectively. All PET scans were performed on a high-resolution research tomograph. Emission data were then acquired over 60 min in list mode as 18 time-frames

Route of Administration: Intravenous

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:15:53 GMT 2023` Edited by `admin` on `Fri Dec 15 16:15:53 GMT 2023`
Record UNII	GF8YTI2N67
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

PK-11195 C-11, R-

Common Name

English

(11C)-(R)-PK 11195

Code

English

(R)-PK-11195 C-11

Common Name

English

1-(2-CHLOROPHENYL)-N-(11C)METHYL-N-((1R))-METHYLPROPYL)ISOQUINOLINE-3-CARBOXAMIDE

Common Name

English

3-ISOQUINOLINECARBOXAMIDE, 1-(2-CHLOROPHENYL)-N-(METHYL-11C)-N-(1-METHYLPROPYL)-, (R)-

Systematic Name

English

Code System Code Type Description

CAS

157727-22-5

Created by admin on Fri Dec 15 16:15:53 GMT 2023 , Edited by admin on Fri Dec 15 16:15:53 GMT 2023

PRIMARY

PUBCHEM

13272375

Created by admin on Fri Dec 15 16:15:53 GMT 2023 , Edited by admin on Fri Dec 15 16:15:53 GMT 2023

PRIMARY

FDA UNII

GF8YTI2N67

Created by admin on Fri Dec 15 16:15:53 GMT 2023 , Edited by admin on Fri Dec 15 16:15:53 GMT 2023

PRIMARY

WIKIPEDIA

PK-11195

Created by admin on Fri Dec 15 16:15:53 GMT 2023 , Edited by admin on Fri Dec 15 16:15:53 GMT 2023

PRIMARY

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PK-11195

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					GF8YTI2N67

PK-11195 C-11, R-

ACTIVE MOIETY

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/8389223 | https://clinicaltrials.gov/ct2/show/NCT00696371 | https://www.ncbi.nlm.nih.gov/pubmed/23715902 | https://www.ncbi.nlm.nih.gov/pubmed/24703991 | https://www.ncbi.nlm.nih.gov/pubmed/22524272

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Approved Use

Doses

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8389223 | https://clinicaltrials.gov/ct2/show/NCT00696371 | https://www.ncbi.nlm.nih.gov/pubmed/23715902 | https://www.ncbi.nlm.nih.gov/pubmed/24703991 | https://www.ncbi.nlm.nih.gov/pubmed/22524272

Drug as perpetrator