The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

AGN-PC-00LSNY     N-butan-2-yl-1-(2- chlorophenyl)-N-methyl...

Synonyms: CHEMBL481537, SureCN117124, AG-H-44208, C0424_SIGMA, CHEBI:73290, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of RP 52028

  • As increasing amounts of unlabeled PK 11195 were added to the radioactive ligand, the myocardial ligand concentration was proportional to myocardial regional perfusion up to quantities of 40 nmol/kg body weight [1].
  • In vitro studies of surgically removed specimens of human glioma demonstrated little binding of Ro5-4864 but high levels of binding of another selective ligand, PK 11195 [2].
  • In addition, prominent bundles of collagen fibers (fibrosis) were commonly found in livers of rats that had been treated with DDC or DDC and PK 11195 [3].
  • We examined the biochemical and ultrastructural alterations in rat liver following experimentally induced acute hepatic porphyria, as well as the effects of the administration of a selective PBR ligand, PK 11195 [3].
  • The increased binding of both ligands correlated to extent of neuronal loss, but only PK 11195 showed correlation to degree of gliosis [4].

Psychiatry related information on RP 52028


High impact information on RP 52028

  • The chemotactic effects of benzodiazepine receptor agonists were blocked by the peripheral benzodiazepine receptor antagonist PK-11195, suggesting that these effects are mediated by the peripheral-type benzodiazepine receptor [7].
  • We conclude that the PK 11195 manifests greater binding than Ro5-4864 to the peripheral-type benzodiazepine binding site on human gliomas and that human gliomas can be successfully imaged using [11C]PK 11195 and PET [2].
  • High affinity binding of isoquinolines, such as PK 11195, is a conserved feature of peripheral-type benzodiazepine receptors (PBR) across species [8].
  • The adrenocorticotropin (ACTH)-responsive Y-1 mouse adrenocortical cell line was used to compare the mechanisms by which ACTH and PK 11195 (a PBR ligand) stimulate steroidogenesis [9].
  • These increases were accounted for by the expression of binding sites with approximate dissociation constants of 5 nM for PK 11195 and 8 nM for Ro5-4864, thereby distinguishing the expressed binding sites as being characteristic of the receptor from rat origin rather than of the host human-derived cell line [10].

Chemical compound and disease context of RP 52028


Biological context of RP 52028

  • With 7-[(dimethylcarbamoyl)oxy]-6-(p-methoxyphenyl)pyrrolo[2,1- d][1,5]benzothiazepine (65), these were the most promising compounds with IC50s of respectively 9, 8, and 9 nM, under conditions where PK 11195 had an IC50 of 2 nM [16].
  • PSC apoptosis was also induced by PK-11195, a ligand of the peripheral benzodiazepine receptor [17].
  • In this same concentration range, PK 11195 and Ro 5-4864, in contrast to clonazepam, induced an accumulation of MCF-7 cells in both the G0-G1 and G2-M phases of the cell cycle [18].
  • After cell exposure to PK 11195 or Ro5-4864 we evidenced typical alterations of apoptotic cell death such as DNA fragmentation and chromatin condensation assessed by flow cytometric and transmission electron microscopy (TEM) analysis, respectively [19].
  • PBR knockdown by RNA inhibition did not affect the proliferation of either cell type and did not influence the inhibitory effect of PK 11195 and Ro5-4864 on cell growth [20].

Anatomical context of RP 52028

  • In vivo, Ro5-4864 increased the initiation of regeneration after a sciatic nerve crush injury and the number of GAP-43-positive axons in the distal nerve while PK 11195 inhibited the enhanced growth produced by a preconditioning lesion [21].
  • The subcellular distribution patterns of specific PK 11195 binding sites were unrelated to the distribution patterns of marker enzymes for plasma membranes, lysosomes, or endoplasmic reticulum [22].
  • When DRG cells were preconditioned into an active growth state by a prior peripheral nerve injury Ro5-4864 augmented and PK 11195, a PBR antagonist, blocked the injury-induced increased outgrowth [21].
  • Further differences between the binding of PK 11195 and Ro5-4864 in astrocytes were detected in the presence of ethanol which was more effective in inhibiting the binding of the latter [23].
  • Inhibition studies in rats following intravenous pre-administration of 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK 11195, 1) showed high specific binding to PBR of [11C]4, [11C]5, and [11C]6 in heart, lung, kidney, adrenal gland, spleen, and brain [24].

Associations of RP 52028 with other chemical compounds


Gene context of RP 52028

  • We have recently reported a significant decrease in the density of BZRP labeled by [3H] PK 11195 in the postmortem brain of chronic schizophrenics, suggesting that dysfunctions of the BZRP are involved in the pathophysiology of schizophrenia [30].
  • Our studies show that PBR expression as measured by PK 11195 ligand binding and Western analysis is much higher in MA-10 cells than R2C cells [31].
  • Moreover, PK-11195 delayed the [Ca2+]i rise induced by TTN but did not significantly affect its extent, and had no effect on the [Ca2+]i rise induced by ENP [32].
  • In vitro inhibition of cellular immune responses by benzodiazepines and PK 11195. Effects on mitogen- and alloantigen-driven lymphocyte proliferation and on IL-1, IL-2 synthesis and IL-2 receptor expression [33].
  • Binding of PK 11195 in both m- and p-fractions from AT-1 tumors, but only in m-fraction from ventral and dorsolateral prostate, was specific, saturable, and of high affinity [34].

Analytical, diagnostic and therapeutic context of RP 52028


  1. Peripheral-type benzodiazepine receptors in the living heart characterized by positron emission tomography. Charbonneau, P., Syrota, A., Crouzel, C., Valois, J.M., Prenant, C., Crouzel, M. Circulation (1986) [Pubmed]
  2. PET imaging of human gliomas with ligands for the peripheral benzodiazepine binding site. Junck, L., Olson, J.M., Ciliax, B.J., Koeppe, R.A., Watkins, G.L., Jewett, D.M., McKeever, P.E., Wieland, D.M., Kilbourn, M.R., Starosta-Rubinstein, S. Ann. Neurol. (1989) [Pubmed]
  3. PK 11195 aggravates 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced hepatic porphyria in rats. Fonia, O., Weizman, R., Coleman, R., Kaganovskaya, E., Gavish, M. Hepatology (1996) [Pubmed]
  4. In vitro quantitative autoradiography of [3H]-L-deprenyl and [3H]-PK 11195 binding sites in human epileptic hippocampus. Kumlien, E., Hilton-Brown, P., Spännare, B., Gillberg, P.G. Epilepsia (1992) [Pubmed]
  5. PET of peripheral benzodiazepine binding sites in the microgliosis of Alzheimer's disease. Groom, G.N., Junck, L., Foster, N.L., Frey, K.A., Kuhl, D.E. J. Nucl. Med. (1995) [Pubmed]
  6. The effects of PK 11195, a ligand for benzodiazepine binding sites, in animal tests of anxiety and stress. File, S.E., Pellow, S. Pharmacol. Biochem. Behav. (1985) [Pubmed]
  7. Benzodiazepine receptor-mediated chemotaxis of human monocytes. Ruff, M.R., Pert, C.B., Weber, R.J., Wahl, L.M., Wahl, S.M., Paul, S.M. Science (1985) [Pubmed]
  8. Cloning and expression of a pharmacologically unique bovine peripheral-type benzodiazepine receptor isoquinoline binding protein. Parola, A.L., Stump, D.G., Pepperl, D.J., Krueger, K.E., Regan, J.W., Laird, H.E. J. Biol. Chem. (1991) [Pubmed]
  9. Peripheral-type benzodiazepine receptors mediate translocation of cholesterol from outer to inner mitochondrial membranes in adrenocortical cells. Krueger, K.E., Papadopoulos, V. J. Biol. Chem. (1990) [Pubmed]
  10. Molecular cloning and expression of cDNA encoding a peripheral-type benzodiazepine receptor. Sprengel, R., Werner, P., Seeburg, P.H., Mukhin, A.G., Santi, M.R., Grayson, D.R., Guidotti, A., Krueger, K.E. J. Biol. Chem. (1989) [Pubmed]
  11. Antiproliferative action of pyrrolobenzoxazepine derivatives in cultured cells: absence of correlation with binding to the peripheral-type benzodiazepine binding site. Zisterer, D.M., Hance, N., Campiani, G., Garofalo, A., Nacci, V., Williams, D.C. Biochem. Pharmacol. (1998) [Pubmed]
  12. Effects of Ro 5-4864 and PK 11195 in rat duodenum and vas deferens. Escubedo, E., Pallas, M., Nuñez, C., Camarasa, J. Eur. J. Pharmacol. (1992) [Pubmed]
  13. Protoporphyrin IX binding and transport by recombinant mouse PBR. Wendler, G., Lindemann, P., Lacapère, J.J., Papadopoulos, V. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  14. Attenuation of ammonia toxicity in mice by PK 11195 and pregnenolone sulfate. Itzhak, Y., Norenberg, M.D. Neurosci. Lett. (1994) [Pubmed]
  15. Interactions between peripheral-type benzodiazepine receptor ligands and an activator of voltage-operated calcium channels. Bolger, G.T., Abraham, S., Oz, N., Weissman, B.A. Can. J. Physiol. Pharmacol. (1990) [Pubmed]
  16. Novel ligands specific for mitochondrial benzodiazepine receptors: 6-arylpyrrolo[2,1-d][1,5]benzothiazepine derivatives. Synthesis, structure-activity relationships, and molecular modeling studies. Fiorini, I., Nacci, V., Ciani, S.M., Garofalo, A., Campiani, G., Savini, L., Novellino, E., Greco, G., Bernasconi, P., Mennini, T. J. Med. Chem. (1994) [Pubmed]
  17. Apoptosis in activated rat pancreatic stellate cells. Klonowski-Stumpe, H., Fischer, R., Reinehr, R., Lüthen, R., Häussinger, D. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  18. Peripheral-type benzodiazepine receptors in the regulation of proliferation of MCF-7 human breast carcinoma cell line. Carmel, I., Fares, F.A., Leschiner, S., Scherübl, H., Weisinger, G., Gavish, M. Biochem. Pharmacol. (1999) [Pubmed]
  19. Peripheral benzodiazepine receptor ligands: mitochondrial transmembrane potential depolarization and apoptosis induction in rat C6 glioma cells. Chelli, B., Lena, A., Vanacore, R., Pozzo, E.D., Costa, B., Rossi, L., Salvetti, A., Scatena, F., Ceruti, S., Abbracchio, M.P., Gremigni, V., Martini, C. Biochem. Pharmacol. (2004) [Pubmed]
  20. Peripheral-type benzodiazepine receptor (PBR) and PBR drug ligands in fibroblast and fibrosarcoma cell proliferation: role of ERK, c-Jun and ligand-activated PBR-independent pathways. Kletsas, D., Li, W., Han, Z., Papadopoulos, V. Biochem. Pharmacol. (2004) [Pubmed]
  21. Role of the peripheral benzodiazepine receptor in sensory neuron regeneration. Mills, C.D., Bitler, J.L., Woolf, C.J. Mol. Cell. Neurosci. (2005) [Pubmed]
  22. Molecular characterization and mitochondrial density of a recognition site for peripheral-type benzodiazepine ligands. Antkiewicz-Michaluk, L., Guidotti, A., Krueger, K.E. Mol. Pharmacol. (1988) [Pubmed]
  23. Characterization of the peripheral-type benzodiazepine receptors in cultured astrocytes: evidence for multiplicity. Itzhak, Y., Baker, L., Norenberg, M.D. Glia (1993) [Pubmed]
  24. Labeling and evaluation of N-[11C]methylated quinoline-2-carboxamides as potential radioligands for visualization of peripheral benzodiazepine receptors. Matarrese, M., Moresco, R.M., Cappelli, A., Anzini, M., Vomero, S., Simonelli, P., Verza, E., Magni, F., Sudati, F., Soloviev, D., Todde, S., Carpinelli, A., Kienle, M.G., Fazio, F. J. Med. Chem. (2001) [Pubmed]
  25. Solubilization of peripheral benzodiazepine-binding sites from rat kidney. Gavish, M., Fares, F. J. Neurosci. (1985) [Pubmed]
  26. "Peripheral-type" binding sites for benzodiazepines in brain: relationship to the convulsant actions of Ro 5-4864. Weissman, B.A., Cott, J., Jackson, J.A., Bolger, G.T., Weber, K.H., Horst, W.D., Paul, S.M., Skolnick, P. J. Neurochem. (1985) [Pubmed]
  27. In vivo and in vitro peripheral-type benzodiazepine receptor polymerization: functional significance in drug ligand and cholesterol binding. Delavoie, F., Li, H., Hardwick, M., Robert, J.C., Giatzakis, C., Péranzi, G., Yao, Z.X., Maccario, J., Lacapère, J.J., Papadopoulos, V. Biochemistry (2003) [Pubmed]
  28. Labelling of "peripheral-type" benzodiazepine binding sites in the rat brain by using [3H]PK 11195, an isoquinoline carboxamide derivative: kinetic studies and autoradiographic localization. Benavides, J., Quarteronet, D., Imbault, F., Malgouris, C., Uzan, A., Renault, C., Dubroeucq, M.C., Gueremy, C., Le Fur, G. J. Neurochem. (1983) [Pubmed]
  29. Identification of a high-affinity peripheral-type benzodiazepine binding site in rat aortic smooth muscle membranes. French, J.F., Matlib, M.A. J. Pharmacol. Exp. Ther. (1988) [Pubmed]
  30. An association study between two missense variations of the benzodiazepine receptor (peripheral) gene and schizophrenia in a Japanese sample. Kurumaji, A., Nomoto, H., Yoshikawa, T., Okubo, Y., Toru, M. Journal of neural transmission (Vienna, Austria : 1996) (2000) [Pubmed]
  31. Regulation of steroid hormone biosynthesis in R2C and MA-10 Leydig tumor cells: role of the cholesterol transfer proteins StAR and PBR. Rao, R.M., Jo, Y., Babb-Tarbox, M., Syapin, P.J., Stocco, D.M. Endocr. Res. (2002) [Pubmed]
  32. Diazepam-binding inhibitor-derived peptides induce intracellular calcium changes and modulate human neutrophil function. Cosentino, M., Marino, F., Cattaneo, S., Di Grazia, L., Francioli, C., Fietta, A.M., Lecchini, S., Frigo, G. J. Leukoc. Biol. (2000) [Pubmed]
  33. In vitro inhibition of cellular immune responses by benzodiazepines and PK 11195. Effects on mitogen- and alloantigen-driven lymphocyte proliferation and on IL-1, IL-2 synthesis and IL-2 receptor expression. Ramseier, H., Lichtensteiger, W., Schlumpf, M. Immunopharmacology and immunotoxicology. (1993) [Pubmed]
  34. Characterization of peripheral benzodiazepine receptors in rat prostatic adenocarcinoma. Batra, S., Alenfall, J. Prostate (1994) [Pubmed]
  35. Isoquinoline and peripheral-type benzodiazepine binding in gliomas: implications for diagnostic imaging. Olson, J.M., Junck, L., Young, A.B., Penney, J.B., Mancini, W.R. Cancer Res. (1988) [Pubmed]
  36. Participation of mitochondrial diazepam binding inhibitor receptors in the anticonflict, antineophobic and anticonvulsant action of 2-aryl-3-indoleacetamide and imidazopyridine derivatives. Auta, J., Romeo, E., Kozikowski, A., Ma, D., Costa, E., Guidotti, A. J. Pharmacol. Exp. Ther. (1993) [Pubmed]
  37. Anxiolytic effects of the neuroactive steroid pregnanolone (3 alpha-OH-5 beta-pregnan-20-one) after microinjection in the dorsal hippocampus and lateral septum. Bitran, D., Dugan, M., Renda, P., Ellis, R., Foley, M. Brain Res. (1999) [Pubmed]
  38. Down-regulation of hepatic peripheral-type benzodiazepine receptors caused by acute lead intoxication. Fonia, O., Weizman, R., Zisman, E., Ashkenazi, R., Gavish, M. Eur. J. Pharmacol. (1995) [Pubmed]
WikiGenes - Universities