In vivo characterization of a novel γ -secretase inhibitor SCH 697466 in rodents and investigation of strategies for managing notch-related side effects

International Journal of Alzheimer's Disease

Volumn 2013, Issue , 2013, Pages

  Hyde, Lynn A ^a   Zhang, Qi ^a   Del Vecchio, Robert A ^a   Leach, Prescott T ^a   Cohen Williams, Mary E ^a   Chen, Lei ^a   Wong, Gwendolyn T ^a   McHugh, Nansie A ^a   Chen, Joseph ^a   Higgins, Guy A ^a   Asberom, Theodros ^a   Li, Wei ^a   Pissarnitski, Dmitri ^a   Levitan, Diane ^a   Nomeir, Amin A ^a   Clader, John W ^a   Zhang, Lili ^a   Parker, Eric M ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; BIOLOGICAL MARKER; GAMMA SECRETASE INHIBITOR; KRUPPEL LIKE FACTOR 4; NOTCH RECEPTOR; SCH 697466; TRANSCRIPTION FACTOR HES 1; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BRAIN CORTEX; BRAIN LEVEL; CEREBROSPINAL FLUID ANALYSIS; CONTROLLED STUDY; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG EXPOSURE; ENTEROPATHY; FEMALE; GENE EXPRESSION; HUMAN; HUMAN CELL; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; RAT; SINGLE DRUG DOSE; THYMUS; THYMUS DISEASE; TREATMENT DURATION;

EID: 84876578172     PISSN: None     EISSN: 20900252     Source Type: Journal    
DOI: 10.1155/2013/823528     Document Type: Article

References (45)

1. Selkoe D. J., The molecular pathology of Alzheimer's disease. Neuron 1991 6 4 487 498 2-s2.0-0025753852 10.1016/0896-6273(91)90052-2
2. Hardy J. A., Higgins G. A., Alzheimer's disease: the amyloid cascade hypothesis. Science 1992 256 5054 184 185 2-s2.0-0026597063
3. Hardy J., Selkoe D. J., The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002 297 5580 353 356 2-s2.0-0037135111 10.1126/science.1072994 (Pubitemid 34790756)
4. Barten D. M., Meredith J. E. Jr., Zaczek R., Houston J. G., Albright C. F., γ -secretase inhibitors for Alzheimer's disease: balancing efficacy and toxicity. Drugs in R and D 2006 7 2 87 97 2-s2.0-33645234720 10.2165/00126839-200607020-00003
5. Hyde L. A., McHugh N. A., Chen J., Zhang Q., Manfra D., Nomeir A. A., Josien H., Bara T., Clader J. W., Zhang L., Parker E. M., Higgins G. A., Studies to investigate the in vivo therapeutic window of the γ -secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2- hydroxyethanoyl]-N1-[(7S)-5-methyl- 6-oxo-6,7-dihydro-5H-dibenzo[b,d] azepin-7-yl]-L-alaninamide (LY411,575) in the CRND8 mouse. Journal of Pharmacology and Experimental Therapeutics 2006 319 3 1133 1143 2-s2.0-33751160615 10.1124/jpet.106.111716
6. Best J. D., Jay M. T., Otu F., Churcher I., Reilly M., Morentin-Gutierrez P., Pattison C., Harrison T., Shearman M. S., Atack J. R., In vivo characterization of A β (40) changes in brain and cerebrospinal fluid using the novel γ -secretase inhibitor N-[cis-4-[(4-chlorophenyl)sulfonyl]-4- (2,5-difluorophenyl)cyclohexyl]-1,1,1- trifluoromethanesulfonamide (MRK-560) in the rat. Journal of Pharmacology and Experimental Therapeutics 2006 317 2 786 790 2-s2.0-33645871592 10.1124/jpet.105.100271
7. Prasad C. V. C., Zheng M., Vig S., Bergstrom C., Smith D. W., Gao Q., Yeola S., Polson C. T., Corsa J. A., Guss V. L., Loo A., Wang J., Sleczka B. G., Dangler C., Robertson B. J., Hendrick J. P., Roberts S. B., Barten D. M., Discovery of (S)-2-((S)-2-(3,5-difluorophenyl)-2-hydroxyacetamido)- N-((S,Z) -3-methyl-4-oxo-4,5-dihydro-3H-benzo[d][1,2]diazepin-5-yl)propanamide (BMS-433796): a γ -secretase inhibitor with A β lowering activity in a transgenic mouse model of Alzheimer's disease. Bioorganic and Medicinal Chemistry Letters 2007 17 14 4006 4011 2-s2.0-34250365682 10.1016/j.bmcl.2007. 04.082 (Pubitemid 46920926)
8. Martone R. L., Zhou H., Atchison- K., Begacestat (GSI-953): a novel, selective thiophene sulfonamide inhibitor of amyloid precursor protein gamma-secretase for the treatment of Alzheimer's disease. Journal of Pharmacology and Experimental Therapeutics 2009 331 2 598 608
9. Gillman K. W., Starrett J. E., Parker M. F., Discovery and evaluation of BMS-708163, a potent, selective and orally bioavailable I ^ 3 -Secretase Inhibitor. ACS Medicinal Chemistry Letters 2010 1 3 120
10. Basi G. S., Hemphill S., Brigham E. F., Amyloid precursor protein selective gamma-secretase inhibitors for treatment of Alzheimer's disease. Alzheimer's Research & Therapy 2010 2 6 36
11. Lanz T. A., Wood K. M., Richter K. E. G., Nolan C. E., Becker S. L., Pozdnyakov N., Martin B. A., Du P., Oborski C. E., Wood D. E., Brown T. M., Finley J. E., Sokolowski S. A., Hicks C. D., Coffman K. J., Geoghegan K. F., Brodney M. A., Liston D., Tate B., Pharmacodynamics and pharmacokinetics of the γ -secretase inhibitor PF-3084014. Journal of Pharmacology and Experimental Therapeutics 2010 334 1 269 277 2-s2.0-77953732993 10.1124/jpet.110.167379
12. Mitani Y., Yarimizu J., Saita K., Uchino H., Akashiba H., Shitaka Y., Ni K., Matsuoka N., Differential effects between gamma-secretase inhibitors and modulators on cognitive function in amyloid precursor protein-transgenic and nontransgenic mice. Journal of Neuroscience 2012 32 6 2037 2050
13. Henley D. B., May P. C., Dean R. A., Siemers E. R., Development of semagacestat (LY450139), a functional γ -secretase inhibitor, for the treatment of Alzheimer's disease. Expert Opinion on Pharmacotherapy 2009 10 10 1657 1664 2-s2.0-67650407720 10.1517/14656560903044982
14. Bateman R. J., Siemers E. R., Mawuenyega K. G., Wen G., Browning K. R., Sigurdson W. C., Yarasheski K. E., Friedrich S. W., DeMattos R. B., May P. C., Paul S. M., Holtzman D. M., A γ -secretase inhibitor decreases amyloid- β production in the central nervous system. Annals of Neurology 2009 66 1 48 54 2-s2.0-66749084437 10.1002/ana.21623
15. Tong G., Wang J. S., Sverdlov O., Multicenter, randomized, double-blind, placebo-controlled, single-ascending dose study of the oral gamma-secretase inhibitor BMS-708163 (Avagacestat): tolerability profile, pharmacokinetic parameters, and pharmacodynamic markers. Clinical Therapeutics 2012 34 3 654 667
16. Fleisher A. S., Raman R., Siemers E. R., Becerra L., Clark C. M., Dean R. A., Farlow M. R., Galvin J. E., Peskind E. R., Quinn J. F., Sherzai A., Sowell B. B., Aisen P. S., Thal L. J., Phase 2 safety trial targeting amyloid beta production with a gamma-secretase inhibitor in Alzheimer disease. Archives of Neurology 2008 65 8 1031 1038
17. Siemers E. R., Quinn J. F., Kaye J., Farlow M. R., Porsteinsson A., Tariot P., Zoulnouni P., Galvin J. E., Holtzman D. M., Knopman D. S., Satterwhite J., Gonzales C., Dean R. A., May P. C., Effects of a γ -secretase inhibitor in a randomized study of patients with Alzheimer disease. Neurology 2006 66 4 602 604 2-s2.0-33645013015 10.1212/01.WNL.0000198762.41312. E1 (Pubitemid 43739900)
18. Best J. D., Smith D. W., Reilly M. A., O'Donnell R., Lewis H. D., Ellis S., Wilkie N., Rosahl T. W., Laroque P. A., Boussiquet-Leroux C., Churcher I., Atack J. R., Harrison T., Shearman M. S., The novel γ secretase inhibitor N-[cis-4-[(4-chlorophenyl)sulfonyl]- 4-(2,5-difluorophenyl)cyclohexyl]-1,1,1- trifluoromethanesulfonamide (MRK-560) reduces amyloid plaque deposition without evidence of notch-related pathology in the Tg2576 mouse. Journal of Pharmacology and Experimental Therapeutics 2007 320 2 552 558 2-s2.0-33846451755 10.1124/jpet.106.114330 (Pubitemid 46147933)
19. Abramowski D., Wiederhold K. H., Furrer U., Jaton A. L., Neuenschwander A., Runser M. J., Danner S., Reichwald J., Ammaturo D., Staab D., Stoeckli M., Rueeger H., Neumann U., Staufenbiel M., Dynamics of A β turnover and deposition in different β -amyloid precursor protein transgenic mouse models following γ -secretase inhibition. Journal of Pharmacology and Experimental Therapeutics 2008 327 2 411 424 2-s2.0-54349097757 10.1124/jpet.108.140327
20. Pollack S. J., Lewis H., γ -Secretase inhibitors for Alzheimer's disease: challenges of a promiscuous protease. Current Opinion in Investigational Drugs 2005 6 1 35 47 2-s2.0-12544258201
21. Lleo A., Saura C. A., gamma-secretase substrates and their implications for drug development in Alzheimer's disease. Current Topics in Medicinal Chemistry 2011 11 12 1513 1527
22. De Strooper B., Annaert W., Cupers P., Saftig P., Craessaerts K., Mumm J. S., Schroeter E. H., Schrijvers V., Wolfe M. S., Ray W. J., Goate A., Kopan R., A presenilin-1-dependent γ -secretase-like protease mediates release of notch intracellular domain. Nature 1999 398 6727 518 522 2-s2.0-0033535504 10.1038/19083 (Pubitemid 29177491)
23. Artavanis-Tsakonas S., Rand M. D., Lake R. J., Notch signaling: cell fate control and signal integration in development. Science 1999 284 5415 770 776 2-s2.0-0033617522 10.1126/science.284.5415.770 (Pubitemid 29291335)
24. Cole D. C., Stock J. R., Kreft A. F., Antane M., Aschmies S. H., Atchison K. P., Casebier D. S., Comery T. A., Diamantidis G., Ellingboe J. W., Harrison B. L., Hu Y., Jin M., Kubrak D. M., Lu P., Mann C. W., Martone R. L., Moore W. J., Oganesian A., Riddell D. R., Sonnenberg-Reines J., Sun S. C., Wagner E., Wang Z., Woller K. R., Xu Z., Zhou H., Jacobsen J. S., (S)-N-(5-Chlorothiophene- 2-sulfonyl)- β β -diethylalaninol a Notch-1-sparing γ -secretase inhibitor. Bioorganic and Medicinal Chemistry Letters 2009 19 3 926 929 2-s2.0-58549088476 10.1016/j.bmcl.2008.11.116
25. Kreft A., Harrison B., Aschmies S., Atchison K., Casebier D., Cole D. C., Diamantidis G., Ellingboe J., Hauze D., Hu Y., Huryn D., Jin M., Kubrak D., Lu P., Lundquist J., Mann C., Martone R., Moore W., Oganesian A., Porte A., Riddell D. R., Sonnenberg-Reines J., Stock J. R., Sun S. C., Wagner E., Woller K., Xu Z., Zhou H., Steven Jacobsen J., Discovery of a novel series of Notch-sparing γ -secretase inhibitors. Bioorganic and Medicinal Chemistry Letters 2008 18 14 4232 4236 2-s2.0-47149093140 10.1016/j.bmcl.2008.05.064
26. Mayer S. C., Kreft A. F., Harrison B., Abou-Gharbia M., Antane M., Aschmies S., Atchison K., Chlenov M., Cole D. C., Comery T., Diamantidis G., Ellingboe J., Fan K., Galante R., Gonzales C., Ho D. M., Hoke M. E., Hu Y., Huryn D., Jain U., Jin M., Kremer K., Kubrak D., Lin M., Lu P., Magolda R., Martone R., Moore W., Oganesian A., Pangalos M. N., Porte A., Reinhart P., Resnick L., Riddell D. R., Sonnenberg-Reines J., Stock J. R., Sun S. C., Wagner E., Wang T., Woller K., Xu Z., Zaleska M. M., Zeldis J., Zhang M., Zhou H., Jacobsen J. S., Discovery of begacestat, a Notch-1-sparing γ -secretase inhibitor for the treatment of Alzheimer's disease. Journal of Medicinal Chemistry 2008 51 23 7348 7351 2-s2.0-57349137219 10.1021/jm801252w
27. Searfoss G. H., Jordan W. H., Calligaro D. O., Galbreath E. J., Schirtzinger L. M., Berridge B. R., Gao H., Higgins M. A., May P. C., Ryan T. P., Adipsin, a biomarker of gastrointestinal toxicity mediated by a functional gamma-secretase inhibitor. Journal of Biological Chemistry 2003 278 46 46107 46116 2-s2.0-0242412482 10.1074/jbc.M307757200 (Pubitemid 37432761)
28. Wong G. T., Manfra D., Poulet F. M., Zhang Q., Josien H., Bara T., Engstrom L., Pinzon-Ortiz M., Fine J. S., Lee H. J. J., Zhang L., Higgins G. A., Parker E. M., Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. Journal of Biological Chemistry 2004 279 13 12876 12882 2-s2.0-11144355129 10.1074/jbc.M311652200 (Pubitemid 38445862)
29. Milano J., McKay J., Dagenais C., Foster-Brown L., Pognan F., Gadient R., Jacobs R. T., Zacco A., Greenberg B., Ciaccio P. J., Modulation of Notch processing by γ -secretase inhibitors causes intestinal goblet cell metaplasia and induction of genes known to specify gut secretory lineage differentiation. Toxicological Sciences 2004 82 1 341 358 2-s2.0-8444247084 10.1093/toxsci/kfh254 (Pubitemid 39485346)
30. Van Es J. H., Van Gijn M. E., Riccio O., Van Den Born M., Vooijs M., Begthel H., Cozijnsen M., Robine S., Winton D. J., Radtke F., Clevers H., Notch/ γ -secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature 2005 435 7044 959 963 2-s2.0-20544460148 10.1038/nature03659 (Pubitemid 40896322)
31. Katoh M., Katoh M., Notch signaling in gastrointestinal tract (Review). International Journal of Oncology 2007 30 1 247 251 2-s2.0-34748828940
32. Zheng H., Pritchard D. M., Yang X., Bennett E., Liu G., Liu C., Ai W., KLF4 gene expression is inhibited by the notch signaling pathway that controls goblet cell differentiation in mouse gastrointestinal tract. American Journal of Physiology 2009 296 3 G490 G498 2-s2.0-65349189620 10.1152/ajpgi.90393.2008
33. Richmond C. A., Breault D. T., Regulation of gene expression in the intestinal epithelium. Progress in Molecular Biology and Translational Science 2010 96 207 229
34. Asberom T., Zhao Z., Bara T. A., Clader J. W., Greenlee W. J., Hyde L. A., Josien H. B., Li W., McPhail A. T., Nomeir A. A., Parker E. M., Rajagopalan M., Song L., Wong G. T., Zhang L., Zhang Q., Pissarnitski D. A., Discovery of γ -secretase inhibitors efficacious in a transgenic animal model of Alzheimer's disease. Bioorganic and Medicinal Chemistry Letters 2007 17 2 511 516 2-s2.0-33846079255 10.1016/j.bmcl.2006.10.011 (Pubitemid 46073732)
35. Chishti M. A., Yang D. S., Janus C., Phinney A. L., Horne P., Pearson J., Strome R., Zuker N., Loukides J., French J., Turner S., Lozza G., Grilli M., Kunicki S., Morissette C., Paquette J., Gervais F., Bergeron C., Fraser P. E., Carlson G. A., George -. P. S., Westawaya D., Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695. Journal of Biological Chemistry 2001 276 24 21562 21570 2-s2.0-0035877756 10.1074/jbc.M100710200 (Pubitemid 37413154)
36. Hyde L. A., Kazdoba T. M., Grilli M., Lozza G., Brussa R., Zhang Q., Wong G. T., McCool M. F., Zhang L., Parker E. M., Higgins G. A., Age-progressing cognitive impairments and neuropathology in transgenic CRND8 mice. Behavioural Brain Research 2005 160 2 344 355 2-s2.0-18044378759 10.1016/j.bbr.2004.12.017 (Pubitemid 40603531)
37. Lanz T. A., Himes C. S., Pallante G., Adams L., Yamazaki S., Amore B., Merchant K. M., The γ -secretase inhibitor N-[N-(3,5-difluorophenacetyl)- lalanyl]-S-phenylglycine t-butyl ester reduces A β levels in vivo in plasma and cerebrospinal fluid in young (plaque-free) and aged (plaque-bearing) Tg2576 mice. Journal of Pharmacology and Experimental Therapeutics 2003 305 3 864 871 2-s2.0-0038476561 10.1124/jpet.102.048280 (Pubitemid 36617962)
38. Barten D. M., Guss V. L., Corsa J. A., Loo A., Hansel S. B., Zheng M., Munoz B., Srinivasan K., Wang B., Robertson B. J., Polson C. T., Wang J., Roberts S. B., Hendrick J. P., Anderson J. J., Loy J. K., Denton R., Verdoorn T. A., Smith D. W., Felsenstein K. M., Dynamics of β -amyloid reductions in brain, cerebrospinal fluid, and plasma of β -amyloid precursor protein transgenic mice treated with a γ -secretase inhibitor. Journal of Pharmacology and Experimental Therapeutics 2005 312 2 635 643 2-s2.0-19944430290 10.1124/jpet.104.075408 (Pubitemid 40189561)
39. Zhang L., Song L., Terracina G., Liu Y., Pramanik B., Parker E., Biochemical characterization of the γ -secretase activity that produces β -amyloid peptides. Biochemistry 2001 40 16 5049 5055 2-s2.0-0035942322 10.1021/bi0028800 (Pubitemid 32332551)
40. Burton C. R., Meredith J. E., Barten D. M., Goldstein M. E., Krause C. M., Kieras C. J., Sisk L., Iben L. G., Polson C., Thompson M. W., Lin X. A., Corsa J., Fiedler T., Pierdomenico M., Cao Y., Roach A. H., Cantone J. L., Ford M. J., Drexler D. M., Olson R. E., Yang M. G., Bergstrom C. P., McElhone K. E., Bronson J. J., Macor J. E., Blat Y., Grafstrom R. H., Stern A. M., Seiffert D. A., Zaczek R., Albright C. F., Toyn J. H., The amyloid- β rise and γ -secretase inhibitor potency depend on the level of substrate expression. Journal of Biological Chemistry 2008 283 34 22992 23003 2-s2.0-53149091309 10.1074/jbc.M804175200
41. Jensen J., Pedersen E. E., Galante P., Hald J., Heller R. S., Ishibashi M., Kageyama R., Guillemot F., Serup P., Madsen O. D., Control of endodermal endocrine development by Hes-1. Nature Genetics 2000 24 1 36 44 2-s2.0-18544404101 10.1038/71657 (Pubitemid 30041417)
42. Fre S., Huyghe M., Mourikis P., Robine S., Louvard D., Artavanis-Tsakonas S., Notch signals control the fate of immature progenitor cells in the intestine. Nature 2005 435 7044 964 968 2-s2.0-20544447734 10.1038/nature03589 (Pubitemid 40896323)
43. Das P., Verbeeck C., Minter L., Chakrabarty P., Felsenstein K., Kukar T., Maharvi G., Fauq A., Osborne B. A., Golde T. E., Transient pharmacologic lowering of Abeta production prior to deposition results in sustained reduction of amyloid plaque pathology. Molecular Neurodegeneration 2012 7 39
44. Lanz T. A., Karmilowicz M. J., Wood K. M., Pozdnyakov N., Du P., Piotrowski M. A., Brown T. M., Nolan C. E., Richter K. E. G., Finley J. E., Fei Q., Ebbinghaus C. F., Chen Y. L., Spracklin D. K., Tate B., Geoghegan K. F., Lau L. F., Auperin D. D., Schachter J. B., Concentration-dependent modulation of amyloid- β in vivo and in vitro using the γ -secretase inhibitor, LY-450139. Journal of Pharmacology and Experimental Therapeutics 2006 319 2 924 933 2-s2.0-33751174340 10.1124/jpet.106.110700
45. Siemers E., Skinner M., Dean R. A., Gonzales C., Satterwhite J., Farlow M., Ness D., May P. C., Safety, tolerability, and changes in amyloid β concentrations after administration of a γ -secretase inhibitor in volunteers. Clinical Neuropharmacology 2005 28 3 126 132 2-s2.0-21544458621 10.1097/01.wnf.0000167360.27670.29 (Pubitemid 40923411)