TSPO ligand residence time: A new parameter to predict compound neurosteroidogenic efficacy

Scientific Reports

Volumn 6, Issue , 2016, Pages

  Costa, Barbara ^a   Da Pozzo, Eleonora ^a   Giacomelli, Chiara ^a   Barresi, Elisabetta ^a   Taliani, Sabrina ^a   Da Settimo, Federico ^a   Martini, Claudia ^a  

^a UNIVERSITY OF PISA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID RECEPTOR; 4 AMINOBUTYRIC ACID RECEPTOR STIMULATING AGENT; 4'-CHLORODIAZEPAM; ANXIOLYTIC AGENT; BENZODIAZEPINE DERIVATIVE; INDOLE DERIVATIVE; ISOQUINOLINE DERIVATIVE; LIGAND; N SEC BUTYL 1 (2 CHLOROPHENYL) N METHYL 3 ISOQUINOLINECARBOXAMIDE; N,N-DI-N-BUTYL-5-CHLORO-2-(4-CHLOROPHENYL)INDOL-3-YLGLYOXYLAMIDE; PREGNENOLONE; PROTEIN BINDING; TRITIUM; TSPO PROTEIN, HUMAN;

BINDING COMPETITION; BIOSYNTHESIS; CYTOLOGY; DOSE RESPONSE; DRUG EFFECTS; GENE EXPRESSION; GENETICS; GLIA; HUMAN; KINETICS; METABOLISM; SECRETION (PROCESS); THERMODYNAMICS; TIME FACTOR; TUMOR CELL LINE;

ANTI-ANXIETY AGENTS; BENZODIAZEPINONES; BINDING, COMPETITIVE; CELL LINE, TUMOR; DOSE-RESPONSE RELATIONSHIP, DRUG; GABA AGONISTS; GENE EXPRESSION; HUMANS; INDOLES; ISOQUINOLINES; KINETICS; LIGANDS; NEUROGLIA; PREGNENOLONE; PROTEIN BINDING; RECEPTORS, GABA; THERMODYNAMICS; TIME FACTORS; TRITIUM;

EID: 84954133252     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep18164     Document Type: Article

References (53)

1. Batarseh, A. & Papadopoulos, V. Regulation of translocator protein 18 kDa (TSPO) expression in health and disease states. Mol. Cell. Endocrinol. 327, 1-12 (2010).
2. Papadopoulos, V. et al. Translocator protein-mediated pharmacology of cholesterol transport and steroidogenesis. Mol. Cell. Endocrinol. 408, 90-98 (2015).
3. Korneyev, A. et al. Stimulation of brain pregnenolone synthesis by mitochondrial diazepam binding inhibitor receptor ligands in vivo. J. Neurochem. 61, 1515-1524 (1993).
4. Romeo, E. et al. Stimulation of brain steroidogenesis by 2-aryl-indole-3-acetamide derivatives acting at the mitochondrial diazepam-binding inhibitor receptor complex. J. Pharmacol. Exp. Ther. 267, 462-471 (1993).
5. Serra M. et al. 2-Phenyl-imidazo[1,2-a]pyridine derivatives as ligands for peripheral benzodiazepine receptors: stimulation of neurosteroid synthesis and anticonflict action in rats. Br. J. Pharmacol. 127, 177-187 (1999).
6. Bitran, D., Foley, M., Audette, D., Leslie, N. & Frye, C. A. Activation of peripheral mitochondrial benzodiazepine receptors in the hippocampus stimulates allopregnanolone synthesis and produces anxiolytic-like effects in the rat. Psychopharmacology. 151, 64-71 (2000).
7. Verleye, M. The anxiolytic etifoxine activates the peripheral benzodiazepine receptor and increases the neurosteroid levels in rat brain. Pharmacol. Biochem. Behav. 82, 712-720 (2005).
8. Yuki, A. et al. Relationship between low free testosterone levels and loss of muscle mass. Sci. Rep. 3, 1818 (2013).
9. Ankrum, J. A., Dastidar, R. G., Ong, J. F., Levy, O. & Karp, J. M. Performance-enhanced mesenchymal stem cells via intracellular delivery of steroids. Sci. Rep. 4, 4645 (2014).
10. Ferzaz, B. et al. SSR180575 (7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide), a peripheral benzodiazepine receptor ligand, promotes neuronal survival and repair. J. Pharmacol. Exp. Ther. 301, 1067-1078 (2002).
11. Girard, C. et al. Etifoxine improves peripheral nerve regeneration and functional recovery. Proc. Natl. Acad. Sci. USA 105, 20505-20510 (2008).
12. Girard, C. Axonal regeneration and neuroinflammation: roles for the translocator protein 18 kDa. Neuroendocrinol. 24, 71-81 (2012).
13. Torres, S. R. Anti-inflammatory effects of peripheral benzodiazepine receptor ligands in two mouse models of inflammation. Eur. J. Pharmacol. 408, 199-211 (2000).
14. Bitran, D., Foley, M., Audette, D., Leslie, N. & Frye, C. A. Activation of peripheral mitochondrial benzodiazepine receptors in the hippocampus stimulates allopregnanolone synthesis and produces anxiolytic-like effects in the rat. Psychopharmacology. 151, 64-71 (2000).
15. Kita, A. et al. Antianxiety and antidepressant-like effects of AC-5216, a novel mitochondrial benzodiazepine receptor ligand. Br. J. Pharmacol. 142, 1059-1072 (2004).
16. Rupprecht, R. et al. Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nat. Rev. Drug. Discov. 9, 971-988 (2010).
17. Da Pozzo, E., Costa, B. & Martini, C. Translocator protein (TSPO) and neurosteroids: implications in psychiatric disorders. Curr. Mol. Med. 12, 426-442 (2012).
18. Costa, B., Da Pozzo, E. & Martini, C. Translocator protein as a promising target for novel anxiolytics. Curr. Top. Med. Chem. 12, 270-285 (2012).
19. Zhang, L. M. et al. Antidepressant-like and anxiolytic-like effects of YL-IPA08, a potent ligand for the translocator protein (18 kDa). Neuropharmacology. 81, 116-125 (2014).
20. Zhang, L. M. et al. Anxiolytic-like effects of YL-IPA08, a potent ligand for the translocator protein (18 kDa) in animal models of post-traumatic stress disorder. Int. J. Neuropsychopharmacol. 17, 1659-69 (2014).
21. Wolf, L. et al. Enhancing neurosteroid synthesis-relationship to the pharmacology of translocator protein (18 kDa) (TSPO) ligands and benzodiazepines. Pharmacopsychiatry. 48, 72-77 (2015).
22. Scarf, A. M., Auman, K. M. & Kassiou, M. Is there any correlation between binding and functional effects at the translocator protein (TSPO) (18 kDa)? Curr. Mol. Med. 12, 387-397 (2012).
23. Morohaku, K. et al. Translocator protein/peripheral benzodiazepine receptor is not required for steroid hormone biosynthesis. Endocrinology. 155, 89-97 (2014).
24. Tu, L. N. et al. Peripheral benzodiazepine receptor/translocator protein global knock-out mice are viable with no effects on steroid hormone biosynthesis. J. Biol. Chem. 289, 27444-27454 (2014).
25. Copeland, R. A. Conformational adaptation in drug-target interactions and residence time. Future. Med. Chem. 3, 1491-1501 (2011).
26. Mollica, L. et al. Kinetics of protein-ligand unbinding via smoothed potential molecular dynamics simulations. Sci. Rep. 5, 11539 (2015).
27. Primofiore, G. et al. N,N-dialkyl-2-phenylindol-3-ylglyoxylamides. A new class of potent and selective ligands at the peripheral benzodiazepine receptor. J. Med. Chem. 47, 1852-1855 (2004).
28. Da Settimo, F. et al. Anxiolytic-like Effects of N,N-Dialkyl-2-phenylindol-3-ylglyoxylamides by Modulation of Translocator Protein Promoting Neurosteroid Biosynthesis. J. Med. Chem. 51, 5798-5806 (2008).
29. Barresi, E. et al. Deepening the Topology of the Translocator Protein Binding Site by Novel N,N-Dialkyl-2-arylindol-3-ylglyoxylamides. J. Med. Chem. 58, 6081-6092 (2015).
30. A receptor activity. Psychoneuroendocrinology. 36, 463-472 (2011).
31. Simorini, F. et al. Medicinal chemistry of indolylglyoxylamide TSPO high affinity ligands with anxiolytic-like effects. Curr. Top. Med. Chem. 12, 333-351 (2012).
32. Motulsky, H. J. & Mahan, L. C. The kinetics of competitive radioligand binding predicted by the law of mass action. Mol. Pharmacol. 25, 1-9 (1984).
33. Sykes, D. A., Dowling, M. R. & Charlton, S. J. Exploring the mechanism of agonist efficacy: a relationship between efficacy and agonist dissociation rate at the muscarinic M3 receptor. Mol. Pharmacol. 76, 543-551 (2009).
34. Guo, D., Mulder-Krieger, T., IJzerman, A. P. & Heitman, L. H. Functional efficacy of adenosine A2A receptor agonists is positively correlated to their receptor residence time. Br. J. Pharmacol. 166, 1846-1859 (2012).
35. Louvel, J. et al. Agonists for the Adenosine A1 Receptor with Tunable Residence Time. A Case for Nonribose 4-Amino-6-aryl-5-cyano-2-thiopyrimidines. J. Med. Chem. 57, 3213-3222 (2014).
36. 3H]PK 11195 binding in rat tubules. FEBS Lett. 169, 138-142 (1984).
37. Olson, J. M. M., Ciliax, B. J., Mandril, W. R. & Young A. B. Presence of peripheral-type benzodiazepine binding sites on human erythrocyte membranes. Eur. J. Pharmacol. 152, 47-53 (1988).
38. Hill, A. V. The mode of action of nicotine and curari, determined by the form of the contraction curve and the method of temperature coefficients. J. Physiol. 39, 361-373 (1909).
39. Motulsky, H. & Christopoulos, A. Analyzing kinetic binding data. In: Fitting models to biological data using linear and nonlinear regression. A practical guide to curve fitting. New-York: Oxford University Press. 245-251 (2003 Eds).
40. Mukhin, A. G., Papadopoulos, V., Costa, E. & Krueger, K. E. Mitochondrial benzodiazepine receptors regulate steroid biosynthesis. Proc. Natl. Acad. Sci. USA 86, 9813-9816 (1989).
41. Papadopoulos, V., Mukhin, A. G., Costa, E. & Krueger, K. E. The peripheral-type benzodiazepine receptor is functionally linked to Leydig cell steroidogenesis. J. Biol. Chem. 265, 3772-3779 (1990).
42. Kozikowski, A. P. et al. Chemistry, binding affinities, and behavioral properties of a new class of "antineophobic" mitochondrial DBI receptor complex (mDRC) ligands. J. Med. Chem. 36, 2908-2920 (1993).
43. Fallahi-Sichani, M., Honarnejad, S., Heiser, L. M., Gray, J. W. & Sorger, P. K. Metrics other than potency reveal systematic variation in responses to cancer drugs. Nat. Chem. Biol. 9, 708-714 (2013).
44. Casarosa, P. et al. Functional and biochemical rationale for 24 h-long duration of action of olodaterol. J. Pharmacol. Exp. Ther. 337, 600-609 (2011).
45. Bernassau, J. M., Reversat, J. L., Ferrara, P., Caput, D. & Lefur, G. A 3D model of the peripheral benzodiazepine receptor and its implication in intra mitochondrial cholesterol transport. J. Mol. Graph., 11, 236-244 (1993).
46. Anzini, M. et al. Mapping and fitting the peripheral benzodiazepine receptor binding site by carboxamide derivatives. Comparison of different approaches to quantitative ligand-receptor interaction modeling. J. Med. Chem. 44, 1134-1150 (2001).
47. Jaremko, L., Jaremko, M., Giller, K., Becker, S. & Zweckstetter, M. Structure of the mitochondrial translocator protein in complex with a diagnostic ligand. Science 343, 1363-1366 (2014).
48. Nguyen, N. et al. Efficacy of etifoxine compared to lorazepam monotherapy in the treatment of patients with adjustment disorders with anxiety: a double-blind controlled study in general practice. Human. Psychopharmacology. 21, 139-149 (2006).
49. Rupprecht, R. et al. Translocator protein (18 kDa) as target for anxiolytics without benzodiazepine-like side effects. Science. 325, 490-493 (2009).
50. Rägo, L. et al. The effect of chronic treatment with peripheral benzodiazepine receptor ligands on behavior and GABAA/benzodiazepine receptors in rat. Naunyn. Schmiedebergs. Arch. Pharmacol. 346, 432-436 (1992).
51. Chelli, B. et al. PK 11195 differentially affects cell survival in human wild-type and 18 kDa Translocator protein-silenced ADF astrocytoma cells. J. Cell. Biochem. 105, 712-723 (2008).
52. Bradford, M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 7, 248-254 (1976).
53. Cheng, Y. & Prusoff, W. H. Relationship between constant (Ki) and the concentration of inhibitor which causes 50% inhibition (IC50) of an enzymatic reaction. Biochem. Pharmacol. 22, 3099-3108 (1973).