PK-11195

Details

Stereochemistry	RACEMIC
Molecular Formula	C21H21ClN2O
Molecular Weight	352.857
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC(C)N(C)C(=O)C1=NC(=C2C=CC=CC2=C1)C3=C(Cl)C=CC=C3

InChI

InChIKey=RAVIZVQZGXBOQO-UHFFFAOYSA-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

HIDE SMILES / InChI

Molecular Formula	C21H21ClN2O
Molecular Weight	352.857
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2992998 | https://www.ncbi.nlm.nih.gov/pubmed/6091832 | https://www.ncbi.nlm.nih.gov/pubmed/27062569 | https://www.ncbi.nlm.nih.gov/pubmed/27544207 | https://www.ncbi.nlm.nih.gov/pubmed/15217830

PK-11195 was first discovered by Pharmuka Laboratories. It was found to be antagonist of the Translocator Protein (TSPO) with potential for development in a number of conditions including cancer models, cardiac ischemia, seizures, depression, and anxiety. PK-11195 has been studied extensively in vitro and in animal models. In phase I clinical trials no anti-inchemic effects were found after drug administration. A tritium [3H] labeled and a C-11 labeled version of PK-11195 are both used diagnostically as PET imaging compounds.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Translocator protein 13 Target ID: P50637 Gene ID: 12257.0 Gene Symbol: Tspo Target Organism: Mus musculus (Mouse) Sources: https://www.ncbi.nlm.nih.gov/pubmed/6330481 \| https://www.ncbi.nlm.nih.gov/pubmed/6325239	Antagonist 2778		2.4 nM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Myocardial ischemia 15 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2992998	Primary	Preclinical	Unknown Approved Use Unknown
Tonic-clonic seizures 7 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6091832	Primary	Preclinical	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27062569	Primary	Basic research	Unknown Approved Use Unknown
Multiple myeloma 159 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15217830	Primary	Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
		252159952
PK 11195 reduces the brain availability of lindane in rats and the convulsions induced by this neurotoxic agent.	1995	7491094
Intrathecally administered flumazenil and PK 11195 precipitate abstinence syndrome in freely moving diazepam dependent rats.	1996 Dec 11	9023073
Expression of the peripheral-type benzodiazepine receptor and apoptosis induction in hepatic stellate cells.	2001 Apr	11266385
Platelet-activating factor induces permeability transition and cytochrome c release in isolated brain mitochondria.	2002 Jul 1	12111814
Melanoma differentiation associated gene-7, mda-7/interleukin-24, induces apoptosis in prostate cancer cells by promoting mitochondrial dysfunction and inducing reactive oxygen species.	2003 Dec 1	14678967
Reversal of Bcl-2-mediated resistance of the EW36 human B-cell lymphoma cell line to arsenite- and pesticide-induced apoptosis by PK11195, a ligand of the mitochondrial benzodiazepine receptor.	2003 Jul	12730627
Involvement of steroids in anti-inflammatory effects of peripheral benzodiazepine receptor ligands.	2004 Jan 30	14706569
Peripheral benzodiazepine receptor ligands induce apoptosis and cell cycle arrest in human hepatocellular carcinoma cells and enhance chemosensitivity to paclitaxel, docetaxel, doxorubicin and the Bcl-2 inhibitor HA14-1.	2004 Nov	15519653
Structure of the Mg-chelatase cofactor GUN4 reveals a novel hand-shaped fold for porphyrin binding.	2005 May	15884974
A novel carbohydrate-based therapeutic GCS-100 overcomes bortezomib resistance and enhances dexamethasone-induced apoptosis in multiple myeloma cells.	2005 Sep 15	16166312
Synthesis, labeling, and biological evaluation of halogenated 2-quinolinecarboxamides as potential radioligands for the visualization of peripheral benzodiazepine receptors.	2006 Jun 15	16495062
Bacterial ortholog of mammalian translocator protein (TSPO) with virulence regulating activity.	2009 Jun 30	19564920
A consecutive three alanine residue insertion mutant of human CAR: a novel CAR ligand screening system in HepG2 cells.	2010 Aug	20686338
Human dosimetry of carbon-11 labeled N-butan-2-yl-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide extrapolated from whole-body distribution kinetics and radiometabolism in rats.	2010 Aug	19941083
Rational quantitative structure-activity relationship (RQSAR) screen for PXR and CAR isoform-specific nuclear receptor ligands.	2010 Dec 5	20869355
Translocator protein (18 kDa) mediates the pro-growth effects of diazepam on Ehrlich tumor cells in vivo.	2010 Jan 25	19782064
Decreases in binding capacity of the mitochondrial 18 kda translocator protein accompany oxidative stress and pathological signs in rat liver after DMBA exposure.	2010 Oct	21037200
Modulation of constitutive androstane receptor (CAR) and pregnane X receptor (PXR) by 6-arylpyrrolo[2,1-d][1,5]benzothiazepine derivatives, ligands of peripheral benzodiazepine receptor (PBR).	2011 Apr 25	21315811
Synthesis of 6-[¹⁸F]fluoro-PBR28, a novel radiotracer for imaging the TSPO 18 kDa with PET.	2011 Aug 15	21741237
Synthesis and evaluation of novel carbon-11 labeled oxopurine analogues for positron emission tomography imaging of translocator protein (18 kDa) in peripheral organs.	2011 Sep 8	21790126
TO901317, a potent LXR agonist, is an inverse agonist of CAR.	2013	23665929
Chrysin, baicalein and galangin are indirect activators of the human constitutive androstane receptor (CAR).	2015 Mar 4	25625231
Improved assays for xenosensor activation based on reverse transfection.	2015 Oct	26187274

Patents

Sample Use Guides

In Vivo Use Guide

Mice received an intraperitoneal injection of PK-11195 (30 - 120 mg/kg ) 30 min before inducing convulsions with one of Ro 5-4864, Ro 5- 3663, PTZ or picrotoxin. Results were mixed. PK-11195 significantly reduced the incidence of convulsions caused by Ro 5-4864 but was ineffective at countering seizures brought on by Ro 5-3663 and picrotoxin. Furthermore, PK 11195 had pro-convulsant actions when combined with sub-convulsant doses of strychnine and picrotoxin.

Route of Administration: Other

In Vitro Use Guide

Human breast cancer cell lines MCF-7 and T47D were cultured and viability and proliferation were determined with a CCK-8 assay. A TSPO selective ligand AC-5216 was added to enhance cellular proliferation and production of allopregnanolone. PK-11195 blocked the effects of AC-5216 with IC50 values of 5.4 nM and 6 nM in MCF-7 and T47D cells respectively.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 10:06:06 GMT 2023` Edited by `admin` on `Sat Dec 16 10:06:06 GMT 2023`
Record UNII	YNF83VN1RL
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PK-11195

Common Name

English

RP-52028

Code

English

PK 11195

Common Name

English

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

Systematic Name

English

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

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID7041097