Novel 5-aryloxypyrimidine SEN1576 as a candidate for the treatment of Alzheimer's disease

International Journal of Neuropsychopharmacology

Volumn 17, Issue 1, 2014, Pages 117-126

  O'Hare, Eugene ^a   Scopes, David I C ^b   Kim, Eun Mee ^c   Palmer, Philip ^a   Spanswick, David ^d,e   McMahon, Bridgeen ^a   Amijee, Hozefa ^b   Nerou, Edmund ^b   Treherne, J Mark ^b   Jeggo, Ross ^e  

^a QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

^b Senexis Limited   (United Kingdom)

^c UNIVERSITY OF ULSTER   (United Kingdom)

^d UNIVERSITY OF WARWICK   (United Kingdom)

^e NEUROSOLUTIONS LTD   (United Kingdom)

Author keywords

Alternating lever cyclic ratio schedule; Alzheimer's disease; amyloid ; long term potentiation; oligomeric A

Indexed keywords

8 FLUORO 4 [5 (3 MORPHOLIN 4 YLPHENOXY)PYRIMIDIN 2 YL] 3,4 DIHYDRO 2H BENZO[1,4]OXAZINE; AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-42]; PYRIMIDINE DERIVATIVE; SEN 1576; UNCLASSIFIED DRUG; AMYLOID BETA-PROTEIN (1-42); NEUROPROTECTIVE AGENT; PEPTIDE FRAGMENT; SEN1576;

ALZHEIMER DISEASE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG CLEARANCE; DRUG PROTEIN BINDING; DRUG STRUCTURE; GUINEA PIG; IN VIVO STUDY; LONG TERM POTENTIATION; MALE; MAXIMUM PLASMA CONCENTRATION; NERVE CELL; NONHUMAN; PRIORITY JOURNAL; RAT; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL CULTURE; CELL SURVIVAL; DOSE RESPONSE; DRUG EFFECTS; INSTRUMENTAL CONDITIONING; INTRACEREBROVENTRICULAR DRUG ADMINISTRATION; METABOLISM;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; CELL SURVIVAL; CELLS, CULTURED; CONDITIONING, OPERANT; DOSE-RESPONSE RELATIONSHIP, DRUG; GUINEA PIGS; INFUSIONS, INTRAVENTRICULAR; LONG-TERM POTENTIATION; MALE; NEURONS; NEUROPROTECTIVE AGENTS; PEPTIDE FRAGMENTS; PYRIMIDINES; RATS;

EID: 84888620396     PISSN: 14611457     EISSN: 14695111     Source Type: Journal    
DOI: 10.1017/S1461145713000886     Document Type: Article

References (36)

1. Amijee H, Scopes DIC (2009) The quest for small molecules as amyloid inhibiting therapies for Alzheimer's disease. J Alzheimer's Dis 17:33-47.
2. Areosa SA, Sherriff F, McShane R (2005) Memantine for dementia. Cocherane Database Syst Rev 20:CD003154.
3. Cleary JP, Walsh DM, Hofmeister JJ, Shankar GM, Kuskowski MA, Selkoe DJ, Ashe KH (2005) Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function. Nat Neurosci 8:79-84. (Pubitemid 41236735)
4. Farlow MR (2002) Do cholinesterase inhibitors slow progression of Alzheimer's disease? Int J Clin Pract Suppl 127:37-44. (Pubitemid 34778529)
5. Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol 8:101-102.
6. Klyubin I, Betts V, Welzel AT, Blennow K, Zetterberg H, Wallin A, Lemere CA, Cullen WK, Peng Y, Wisniewski T, Selkoe DJ, Anwyl R, Walsk DM, Rowan MJ (2008) Amyloid beta protein dimer-containing human CSF disrupts synaptic plasticity: prevention by systemic passive immunization. J Neurosci 28:4231-4237.
7. LeVine H III (1999) Quantification of beta-sheet amyloid fibril structures with thioflavin T. Methods Enzymol 309:274-284.
8. Nakagami Y, Nishimura S, Murasugi T, Kenko I, Meguro M, Marumoto S, Kogen H, Koyama K, Oda T (2002) A novel β-sheet breaker, RS-0406, reverses amyloid β-induced cytotoxicity and impairment of long-term potentiation in vitro. Br J Pharmacol 137:676-682. (Pubitemid 35333093)
9. O'Hare E, Scopes DIC, Treherne JM, Norwood K, Spanswick D, Kim E-M (2010) RS-0406 arrests amyloid-β oligomer-induced behavioral deterioration in vivo. Behav Brain Res 210:32-37.
10. O'Hare E, Scopes DIC, Kim E-M, Palmer P, Jones M, Whyment AD, Spanswick D, Amijee H, Nerou E, McMahon B, Treherne JM, Jeggo R (2013) Orally bioavailable small molecule drug protects memory in Alzheimer's disease models. Neurobiol Aging 34:1116-1125.
11. Ondrejcak T, Klyubin I, Hu NW, Barry AE, Cullen WK, Rowan MJ (2010) Alzheimer's disease amyloid beta-protein and synaptic function. Neuromolecular Med 12:13-26.
12. Parsons CG, Danysz W, Quack G (1999) Memantine is a clinically well tolerated NMDA receptor antagonist-a review of preclinical data. Neuropsychopharmacology 38:735-767. (Pubitemid 29187336)
13. Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. 4th edn. New York: Academic Press.
14. Pharm E, Crews L, Ubhi K, Hansen L, Adame A, Cartier A, Salmon D, Galasko D, Michael S, Savas JN, Yates JR, Glabe C, Masliah E (2010) Progressive accumulation of amyloid-beta oligomers in Alzheimer's disease and in amyloid precursor protein transgenic mice is accompanied by selective alterations in synaptic scaffold proteins. FEBS J 277:3051-3067.
15. Podlisny MB, Ostaszewski BL, Squazzo SL, Koo EH, Rydell RE, Teplow DB, Selkoe DJ (1995) Aggregation of secreted amyloid beta protein into sodium dodecyl sulphate-stable oligomers in cell culture. J Biol Chem 270:9564-9570.
16. Podlisny MB, Walsh DM, Amorante P, Ostaszewski BL, Stimson ER, Maggio JE, Teplow DB, Selkoe DJ (1998) Oligomerization of endogenous and synthetic amyloid beta protein at nanomolar levels in cell culture and stabilization of monomer by Congo red. Biochemistry 37:3602-3611. (Pubitemid 28162915)
17. Poling A, Morgan-Paisley KP, Panos JJ, Kim E-M, O'Hare E, Cleary JP, Lesne S, Ashe KH, Porritt M, Baker LE (2008) Oligomers of the amyloid beta-beta protein disrupt working memory: confirmation with two behavioral procedures. Behav Brain Res 193:230-234.
18. Portelius E, Olsson M, Brinkmalm G, Ruetschi U, Mattsson N, Andreasson U, Gobom J, Brinkmalm A, Holtta M, Blennow K, Zetterberg H (2013) Mass spectrometric characterization of amyloid-β species in the 7PA2 cell model of Alzheimer's disease. J Alzheimers Dis 33:85-93.
19. Raschetti R, Albanese E, Vanacore N, Magginin M (2007) Cholinesterase inhibitors in mild cognitive impairment: a systematic review of randomised trials. PLoS Med 4:e338.
20. Reed MN, Hofmeister JJ, Jungbauer L, Welzel AT, Yu C, Sherman MA, Lesne S, LaDu MJ, Walsh DM, Ashe KH, Cleary JP (2011) Cognitive effects of cell-derived and synthetically derived Aβ oligomers. Neurobiol Aging 32:1784-1794.
21. Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius HJ (2003) Memantine in moderate-to-severe Alzheimer's disease. N Eng J Med 348:1333-1341. (Pubitemid 36384100)
22. Schneider LS, Dagermans KS, Higgins JP, McShane R (2011) Lack of evidence for the efficacy of Memantine in mild Alzheimer's disease. Arch Neurol 68:991-998.
23. Scopes DIC, O'Hare E, Jeggo R, Whyment AD, Spanswick D, Kim E-M, Gannon J, Amijee H, Treherne JM. (2012) Aβ oligomer toxicity inhibitor protects memory in models of synaptic toxicity. Br J Pharmacol 167:383-392.
24. Shah S, Reichman WE (2006) Treatment of Alzheimer's disease across the spectrum of severity. Clin Interv Aging 1:131-142.
25. Shankar GM, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, Regan CM, Walsh DM, Sabatini BL, Selkoe DJ (2008) Amyloid-β protein dimers isolated directly from Alzheimer's brain impair synaptic plasticity and memory. Nat Med 14:837-842.
26. Shankar GM, Welzel AT, McDonald JM, Selkoe DJ, Walsh DM (2011) Isolation of low-n amyloid β-protein oligomers from cultured cells, CSF, and brain. Methods Mol Biol 670:33-44.
27. Shearman MS, Hawtin SR, Tailor VJ (1995) The intracellular component of cellular 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) reduction is specifically inhibited by beta-amyloid peptides. J Neurochem 65:218-227.
28. Tanzi RE, Moir RD, Wagner SL (2007) Clearance of Alzheimer's Abeta peptide: the many roads to perdition. Neuron 43:605-608. (Pubitemid 39179722)
29. Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I (2004) Memantine treatment in patients with moderate to severe Alzheimer's disease already receiving donepezil: a randomized control trial. JAMA 291:317-324. (Pubitemid 38101604)
30. Townsend M, Cleary JP, Mehta T, Hofmeister J, Lesne S, O'Hare E, Walsh DM, Selkoe DJ (2006) Orally available compound prevents deficits in memory caused by the Alzheimer amyloid-beta oligomers. Ann Neurol 60:668-676. (Pubitemid 46048484)
31. Walsh DM, Selkoe DJ (2007) Aβ oligomers-a decade of discovery. J Neurochem 101:1172-1184.
32. Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS (2002) Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416:535-539. (Pubitemid 34288854)
33. Walsh DM, Klyubin I, Shankar GM, Townsend M, Fadeeva JV, Betts V, Podlisny MB, Cleary JP, Ashe KH, Rowan MJ, Selkoe DJ (2005a) The role of cell-derived oligomers of Abeta in Alzheimer's disease and avenues for therapeutic intervention. Biochem Soc Trans 33:1087-1090. (Pubitemid 41659119)
34. Walsh DM, Townsend M, Podlisny MB, Shankar GM, Fadeeva JV, El-Agnaf O, Hartley DM, Selkoe DJ (2005b) Certain inhibitors of synthetic amyloid β-peptide (Aβ) fibrillogenesis block oligomerization of natural Aβ and thereby rescue long-term potentiation. J Neurosci 25:2455-2462. (Pubitemid 40365155)
35. Wang Q, Walsh DM, Rowan MJ, Selkoe DJ, Anwyl R (2004) Block of long-term potentiation by naturally secreted and synthetic amyloid β-peptide in hippocampal slices is mediated via activation of the kinases c-jun N-terminal kinase, cyclin-dependent kinase 5, and p38 mitogen-activated protein kinase as well as metabotropic glutamate receptor type 5. J Neurosci 24:3370-3378. (Pubitemid 38451902)
36. Weldon DT, O'Hare E, Kuskowski MA, Cleary J, Mach JR (1996) Alternating-lever cyclic-ratio schedule analysis of the effects of atropine sulfate. Pharmacol Biochem Behav 54:753-757. (Pubitemid 26258660)