85532-75-8 Usage
Uses
Used in Pharmaceutical Industry:
PK-11195 is used as a high affinity peripheral benzodiazepine receptor (PBR) ligand for regulating protein phosphorylation in rat brain mitochondria under the control of Ca2+. It promotes mitochondrial apoptosis and blocks P-glycoprotein (Pgp)-mediated drug efflux to chemosensitize cancer cells, enhancing the effectiveness of various chemotherapeutic agents.
Biological Activity
Possesses high affinity for the MDR (peripheral benzodiazepine receptor) without binding to other known neurotransmitter receptors.
Biochem/physiol Actions
PK 11195 is a peripheral benzodiazepine antagonist. It is also an antagonist for human constitutive androstane receptor (hCAR) and human pregnane X receptor (PXR). In human primary hepatocytes, PK 11195 upon demethylation elicits agonist functionality towards the receptor hCAR. PK 11195 also antagonise B-cell lymphoma 2 (Bcl-2) and may serve as a potential compound for mitochondrial targeting therapies and in the treatment of cholangiocarcinoma.
References
1) Le Fur, et al.; (1983) Peripheral benzodiazepine binding sites: effect of PK 11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide. I. In vitro studies; Life Sci., 32 1839
2) Le Fur et al.; (1983) Peripheral benzodiazepine binding sites: effect of PK 11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide. II. In vivo studies; Life Sci., 32 1849
3) Gonzalez-Polo et al. (2005) PK11195 potently sensitizes to apoptosis induction independently from the peripheral benzodiazepine receptor; Oncogene, 24 7503
4) Walter et al. (2005) PK11195, a peripheral benzodiazepine receptor (pBR) ligand, broadly blocks drug efflux to chemosensitize leukemia and myeloma cells by a pBR-independent, direct transporter-modulating mechanism; Blood, 106 3584
5) Chelli et al. (2004) Peripheral benzodiazepine receptor ligands:mitochondrial transmembrane potential depolarization and apoptosis induction in rat C6 glioma cells; Biochem. Pharmacol., 68 125
6) Sutter et al. (2004) 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; J. Hepatol., 120 1212
7) Maaser et al. (2001) Specific ligands of the peripheral benzodiazepine receptor induce apoptosis and cell cycle arrest in human colorectal cancer cells; Br. J. Cancer, 85 1771
Check Digit Verification of cas no
The CAS Registry Mumber 85532-75-8 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,5,5,3 and 2 respectively; the second part has 2 digits, 7 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 85532-75:
(7*8)+(6*5)+(5*5)+(4*3)+(3*2)+(2*7)+(1*5)=148
148 % 10 = 8
So 85532-75-8 is a valid CAS Registry Number.
InChI:InChI=1/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
85532-75-8Relevant academic research and scientific papers
A novel approach for the synthesis of the peripheral benzodiazepine receptor ligand, PK11195
Stevenson, Louise,Pimlott, Sally L.,Sutherland, Andrew
, p. 7137 - 7139 (2008/03/11)
A new synthesis of the peripheral benzodiazepine receptor ligand, PK11195 has been developed in only six-steps using a Heck-type reaction and a Suzuki coupling to effect the key transformations. The flexibility of this new approach is demonstrated by the
Derivatives of arene and hetero-arene carboxamides and their use as medicaments
-
, (2008/06/13)
Compounds with the formula: STR1 in which R 1 and R 2 represent independently, a linear or branched alkyl, cycloalkyl, phenylalkyl or cycloalkylalkyl group. R 1 and R 2 may also represent an alkenyl or alkynyl group. R 1 and R 2 may also represent a group
