(R)-flurbiprofen - An enantiomer of flurbiprofen for the treatment of Alzheimer's disease

IDrugs

Volumn 10, Issue 2, 2007, Pages 121-133

  Geerts, Hugo ^a  

^a In Silico Biosciences   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID; AMYLOID BETA PROTEIN[1-42]; AMYLOID PRECURSOR PROTEIN; ATORVASTATIN; CHOLINESTERASE INHIBITOR; CYCLOOXYGENASE 2 INHIBITOR; DEXAMETHASONE; DONEPEZIL; FLUINDOSTATIN; FLURBIPROFEN; GALANTAMINE; GAMMA SECRETASE; GAMMA SECRETASE INHIBITOR; HOMOTAURINE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IBUPROFEN; INDOMETACIN; KETOPROFEN; LY 450139; MEMANTINE; NONSTEROID ANTIINFLAMMATORY AGENT; PLACEBO; PROSTAGLANDIN SYNTHASE; RIVASTIGMINE; SEROTONIN UPTAKE INHIBITOR; UNCLASSIFIED DRUG; ZOLMITRIPTAN;

ALZHEIMER DISEASE; AMINO TERMINAL SEQUENCE; ANEMIA; AREA UNDER THE CURVE; ARTICLE; BEHAVIOR; CLINICAL TRIAL; COGNITION; DIARRHEA; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG CLEARANCE; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG FORMULATION; DRUG MECHANISM; DRUG METABOLISM; DRUG SCREENING; DRUG WITHDRAWAL; DUODENUM INJURY; DYSPEPSIA; ENANTIOMER; ENZYME INHIBITION; EOSINOPHILIA; GASTROINTESTINAL DISEASE; GENERAL SOMATIC DISORDER; HEARTBURN; HUMAN; IN VITRO STUDY; INCIDENCE; LOWER RESPIRATORY TRACT INFECTION; MENTAL DISEASE; MENTAL PATIENT; MENTAL PERFORMANCE; MUSCLE CRAMP; NEUROLOGIC DISEASE; NONHUMAN; PAW EDEMA; PROSTATE CANCER; PSYCHIATRY; SINGLE DRUG DOSE; STATISTICAL SIGNIFICANCE; STOMACH EROSION; STRUCTURE ACTIVITY RELATION; SUBMUCOSAL HEMORRHAGE; ANIMAL; CHEMISTRY; MALE; PATENT; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PHASE 3 CLINICAL TRIAL; PROSTATE TUMOR; REVIEW; STEREOISOMERISM;

ALZHEIMER DISEASE; ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; CLINICAL TRIALS, PHASE I; CLINICAL TRIALS, PHASE II; CLINICAL TRIALS, PHASE III; FLURBIPROFEN; HUMANS; MALE; PATENTS; PROSTATIC NEOPLASMS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33947315426     PISSN: 13697056     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (90)

1. Stereoselective disposition of flurbiprofen in normal volunteers. Knadler MP, Brater DC, Hall SD BR J CLIN PHARMACOL 1992 33 4 369-375
2. Variability of inversion of (R)-flurbiprofen in different species. Menzel-Soglowek S, Geisslinger G, Beck WS, Brune K J PHARM SCI 1992 81 9 888-891
3. Rac-flurbiprofen is more ulcerogenic that its (S)-enantiomer. Wechter WJ, Bigornia AE, Murray Jr ED, Levine BH, Young JW CHIRALITY 1993 5 7 492-494
4. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group. Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff LT NEUROLOGY 1998 50 1 136-145
5. Stereoselective inhibition of inducible cyclooxygenase by chiral nonsteroidal anti-inflammatory drugs. Carabaza A, Cabre F, Rotlan E, Gomez M, Gutierrez M, Garcia ML, Mauleon D J CLIN PHARMACOL 1996 36 6 505-512
6. Encore licenses cancer compound to Myriad Genetics. Encore Pharmaceuticals Inc PRESS RELEASE 1999 April 15
7. PK-guided multi-dose, tolerance and safety of E-7869 in prostate cancer patients. Quiggle DD, Lilly M, Murray ED, Gibson KM, Leipold DD, Guiterrez I, Loughman BE, Wechter WJ PROC AM ASSOC CANCER RES 2000 41 April 1-5 Abs 3874
8. Phase I single-dose pharmacokinetics and lack of enanthiomeric bioinverson of E-7869 (R-flurbiprofen). Murray ED, Quiggle D, Gibson K, Leipold D, Loughman B, Wechter W CLIN PHARMACOL THER 2000 67 2 PI-56
9. Treatment and survival study in the C57BL/6J-APC(Min)/+(Min) mouse with R-flurbiprofen. Wechter WJ, Murray EDJ, Kantoci D, Quiggle DD, Leipold DD, Gibson KM, McCracken JD LIFE SCI 2000 66 8 745-753
10. Encore Pharmaceuticals licenses lead cancer compound to Myriad Genetics. Encore Pharmaceuticals Inc PRESS RELEASE 2000 December 08
11. Myriad Genetics acquires exclusive rights to cancer drug in phase II human clinical trials: Acquisition moves Myriad's therapeutic development program well downstream toward commercialization. Myriad Genetics Inc PRESS RELEASE 2000 December 08
12. Multi-dose phase I-II trial of E-7869 in prostate cancer patients: Safety and time-to-PSA progression (TPSAP). Lilly M, Ruckle H, Quiggle D, Gutierrez I, Murray ED, Gibson K, Leipold D, Wechter WJ, Loughman B PROC AM ASSOC CANCER RES 2001 42 March 24-28 Abs 763
13. 42 independently of cyclooxygenase activity. Weggen S, Eriksen JL, Das P, Sagi SA, Wang R, Pietrzik CU, Findlay KA, Smith TE, Murphy MP, Bulter T, Kang DE et al NATURE 2001 414 6860 212-216
14. Multi-dose phase IIa trial of MPC-7869 in prostate cancer patients with increasing prostate-specific antigen (PSA). Swabb EA, Quiggle DD, Gutierrez I, Murray Jr ED, Reid JE, Wechter WJ, Loughman BE PROC AM ASSOC CANCER RES 2002 43 Abs 3714
15. Induction of CYP2C genes in human hepatocytes in primary culture. Gerbal-Chaloin S, Pascussi JM, Pichard-Garcia L, Daujat M, Waechter F, Fabre JM, Carrere N, Maurel P DRUG METAB DISPOS 2001 29 3 242-251
16. Taro Pharmaceuticals reports record 2002 results. Taro Pharmaceutical Industries Ltd PRESS RELEASE 2003 February 20
17. Myriad Genetics initiates enrollment in phase II Alzheimer's drug trial. Myriad Genetics Inc PRESS RELEASE 2003 June 25
18. Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. Wolfe NM, Lichtenstein DR, Singh G N ENGL J MED 1999 340 24 1888-1899
19. 42 in vivo. Eriksen JL, Sagi SA, Smith TE, Weggen S, Das P, McLendon DC, Ozols VV, Jessing KW, Zavitz KH, Koo EH, Golde TE J CLIN INVEST 2003 112 3 440-449
20. Myriad Genetics Inc - 2003 Annual Report. Myriad Genetics Inc ANNUAL REPORT 2003 August 25
21. NC-531 (Neurochem). Geerts H CURR OPIN INVESTIG DRUGS 2004 5 1 95-100
22. Good safety results for Myriad's Flurizan in AD. Myriad Genetics Inc PRESS RELEASE 2004 July 20
23. Inhibition of noxious stimulus-induced spinal prostaglandin E2 release by flurbiprofen enantiomers: A microdialysis study. Geisslinger G, Muth-Selbach U, Coste O, Vetter G, Schroedter A, Schaible HG, Brune K, Tegeder I J NEUROCHEM 2000 74 5 2094-2100
24. R-flurbiprofen suppresses LS-174T xenograft growth in the nude rat. McCracken JD, Godil A, Murray ED, Kantoci D, Gridley D, Andres M, Langridge W, Pant KD, Wechter WJ PROC AM ASSOC CANCER RES 1998 39 314 Abs 2146
25. Clinical endoscopic evaluation of the gastroduodenal tolerance to (R)-ketoprofen, (R)-flurbiprofen, racemic ketoprofen, and paracetamol: A randomized, single-blind, placebo-controlled trial. Jerussi TP, Caubet JF, McCray JE, Handley DA J CLIN PHARMACOL 1998 38 2 Suppl 19S-24S
26. 42 production by NSAID R-enantiomers. Morihara T, Chu T, Ubeda O, Beech W, Cole GM J NEUROCHEM 2002 83 4 1009-1012
27. Comparison of celecoxib with NS-398, sulindac, and R-flurbiprofen on suppression of human hepatocellular carcinoma (HCC) cell proliferation. Hu KQ, Yu CH HEPATOLOGY 2002 36 4
28. Synthesis of (R)-flurbiprofen via enzymatic asymmetric decarboxylation. Terao Y, Ijima Y, Kakidani H, Ohta H J MOL CATAL B ENZYMATIC 2002 18 1-3 177
29. Induction of cell cycle arrest and apoptosis in colon cancer cells by S-and R-flurbiprofen. Groesch S, Schilling K, Tegeder I, Niederberger E, Geisslinger G NAUNYN SCHMIEDEBERGS ARCH PHARMACOL 2002 365 Suppl 1 R118
30. Inhibition of NFκB and AP-1 activation by R- and S-flurbiprofen. Tegeder I, Niederberger E, Israr E, Guehring H, Brune K, Euchenhofer C, Groesch S, Geisslinger G FASEB J 2001 15 3 595-597
31. Chronic treatment of transgenic APP mice with R-flurbiprofen. Eriksen JL, Nicolle MM, Prescott S, Ozols VV, Zhuo JM, Monnier TE, Beard JL, Weggen S, Sagi SA, Koo EH, Golde TE AM SOC NEUROSCI 2003 Abs 295.22
32. Long-term, but not short-term, R-flurbiprofen treatment ameliorates cognitive deficits in transgenic APP mice. Nicolle MM, Prescott S, Murphy MP, Kukar T, Eriksen JL, Koo EH, Golde TE ABSTR SOC NEUROSCI 2004 34 Abs 674.6
33. Myriad Genetics initiates phase 3 clinical trial of Flurizan™ in Alzheimer's disease. Myriad Genetics Inc PRESS RELEASE 2005 January 12
34. A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Tuszynski MH, Thal L, Pay M, Salmon DP, U HS, Bakay R, Patel P, Blesch A, Vahlsing HL, Ho G, Tong G et al NAT MED 2005 11 5 551-555
35. Myriad's AD therapy shows promise despite failing phase II endpoints. Myriad Genetics Inc PRESS RELEASE 2005 May 02
36. Myriad Genetics presents results of phase 2 trial of Flurizan™ in patients with Alzheimer's disease. Myriad Genetics Inc PRESS RELEASE 2005 June 21
37. Myriad phase III Alzheimer's trial given FDA OK to proceed. Myriad Genetics Inc PRESS RELEASE 2005 August 02
38. Differential increase in cerebrospinal fluid-acetylcholinesterase after treatment with acetylcholinesterase inhibitors in patients with Alzheimer's disease. Davidsson P, Blennow K, Andreasen N, Eriksson B, Minthon L, Hesse C NEUROSCI LETT 2001 300 3 157-160
39. 42-lowering agent Flurizan in patients with mild to moderate Alzheimer's disease: Efficacy, safety and follow-on study results. Black S, Wilcock G, Haworth J, Hendrix S, Zavitz K, Binger M, Roch J, Laughlin M, Swabb E, Hobden A ABSTR SOC NEUROSCI 2005 35 Abs 586.6
40. Myriad's 24-month study of Flurizan demonstrates significant benefit in Alzheimer's disease patients. Myriad Genetics Inc PRESS RELEASE 2006 July 19
41. Myriad completes recruitment in phase III Flurizan trial in AD. Myriad Genetics Inc PRESS RELEASE 2006 August 22
42. 42-lowering agent, in Alzheimer's disease (AD): Results of a 12-month phase 2 trial and 1-year follow-on study. Laughlin M, Black SE, Wilcock GK, Haworth J, Hendrix S, Zavitz KH, Christensen D, Binger M, Bass S, Edward S J AM GERIATR SOC 2006 54 4 Abs P18
43. R-flurbiprofen protects neuronal cells from amyloid-β toxicity in concert with an upregulation of gene expression and secretion of nerve growth factor (NGF). Andrews PM, Allen JD, Rebeck GW, Hoe HS, Sorkin GC, Chang ML, Li F NEUROLOGY 2006 66 5 Suppl 2 278
44. A phase II study targeting amyloid-β with 3APS in mild-to-moderate Alzheimer disease. Aisen PS, Saumier D, Briand R, Laurin J, Gervais F, Tremblay P, Garceau D NEUROLOGY 2006 67 10 1757-1763
45. Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer's disease? The Rotterdam study. Andersen K, Launer LJ, Ott A, Hoes AW, Breteler MM, Hofman A NEUROLOGY 1995 45 8 1441-1445
46. Enzymatic synthesis of (R)-flurbiprofen. Terao Y, Ijima Y, Kakidani H, Ohta H BULL CHEM SOC JPN 2003 76 12 2395-2397
47. The novel γ-secretase inhibitor MRK-560 reduces amyloid plaque deposition without evidence of Notch-related pathology in the Tg2576 mouse. Best JD, Smith DW, Reilly MA, O'Donnell R, Lewis HD, Ellis S, Wilkie N, Rosahl TW, Laroque P, Boussiquet-Leroux C, Churcher I et al J PHARMACOL EXP THER 2007 320 2 552-558
48. Inflammatory mechanisms in Alzheimer's disease: Inhibition of the β-amyloid stimulated pro-inflammatory responses and neurotoxicity by PPARγ antagonists. Combs C, Johnson D, Karlo J, Cannady S, Landreth GJ NEUROSCI 2000 20 2 558-567
49. Effect of the enantiomers of flurbiprofen, ibuprofen, and ketoprofen on intestinal permeability. Davies NM, Wright MR, Russell AS, Jamali F J PHARM SCI 1996 85 11 1170-1173
50. Reduction of Aβ levels in the Sprague Dawley rat after oral administration of the functional γ-secretase inhibitor DAPT: A novel nontransgenic model for Aβ production inhibitors. El Mouedden M, Vandermeeren M, Meert T, Mercken M CURR PHARM DES 2006 12 6 671-676
51. Two-year follow-up of amyloid deposition in patients with Alzheimer's disease. Engler H, Forsberg A, Almkvist O, Blomquist G, Larsson E, Savitcheva I, Wall A, Ringheim A, Langstrom B, Nordberg A BRAIN 2006 129 11 2856-2866
52. Stereoselective pharmacokinetics of flurbiprofen in humans and rats. Jamali F, Berry BW, Tehrani MR, Russell AS J PHARM SCI 1988 77 8 666-669
53. Plasma protein binding of flurbiprofen: Enantioselectivity and influence of pathophysiological status. Knadler MP, Brater DC, Hall SD J PHARMACOL EXP THER 1989 249 2 378-385
54. 42 production. Kukar T, Murphy MP, Eriksen JL, Sagi SA, Weggen S, Smith TE, Ladd T, Khan MA, Kache R, Beard J, Dodson M et al NAT MED 2005 11 5 545-550
55. Ibuprofen inhibits survival of bladder cancer cells by induced expression of the p75NTR tumor suppressor protein. Khwaja F, Allen J, Lynch J, Andrews P, Djakiew D CANCER RES 2004 64 17 6207-6213
56. Bioinversion of R-flurbiprofen to S-flurbiprofen at various dose levels in rat, mouse, and monkey. Leipold DD, Kantoci D, Murray ED Jr, Quiggle DD, Wechter WJ CHIRALITY 2004 16 6 379-387
57. Targeting the β-catenin/APC pathway: A novel mechanism to explain the cyclooxygenase-2-independent anticarcinogenic effects of celecoxib in human colon carcinoma cells. Maier TJ, Janssen A, Schmidt R, Geisslinger G, Grosch S FASEB J 2005 19 10 1353-1355
58. Inflammation, anti-inflammatory agents and Alzheimer disease: The last 12 years. McGeer PL, Rogers J, McGeer EG J ALZHEIMERS DIS 2006 9 3 271-276
59. 11C]PIB in a nondemented population: Potential antecedent marker of Alzheimer disease. Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC NEUROLOGY 2006 67 3 446-452
60. Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer's disease. Oddo S, Caccamo A, Kitazawa M, Tseng BP, LaFerla FM NEUROBIOL AGING 2003 24 8 1063-1070
61. Plasma levels of β-amyloid (1-42) in Alzheimer's disease and mild cognitive impairment. Pesaresi M, Lovati C, Bertora P, Mailland E, Galimberti D, Scarpini E, Quadri P, Forloni G, Mariani C NEUROBIOL AGING 2006 27 6 904-905
62. Acetylcholinesterase promotes β-amyloid plaques in cerebral cortex. Rees T, Hammond PI, Soreq H, Younkin S, Brimijoin S NEUROBIOL AGING 2003 24 6 777-787
63. Rofecoxib: No effect on Alzheimer's disease in a 1-year, randomized, blinded, controlled study. Reines SA, Block GA, Morris JC, Liu G, Nessly ML, Lines CR, Norman BA, Baranak CC NEUROLOGY 2004 62 1 66-71
64. Clinical trial of indomethacin in Alzheimer's disease. Rogers J, Kirby LC, Hempelman SR, Berry DL, McGeer PL, Kaszniak AW, Zalinski J, Cofield M, Mansukhani L, Willson P, Kogan F NEUROLOGY 1993 43 8 1609-1611
65. Effects of a γ-secretase inhibitor in a randomized study of patients with Alzheimer disease. Siemers ER, Quinn JF, Kaye J, Farlow MR, Porsteinsson A, Tariot P, Zoulnouni P, Galvin JE, Holtzman DM, Knopman DS, Satterwhite J et al NEUROLOGY 2006 66 4 602-604
66. Circulating cholesterol levels, apolipoprotein E genotype and dementia severity influence the benefit of atorvastatin treatment in Alzheimer's disease: Results of the Alzheimer's Disease Cholesterol-Lowering Treatment (ADCLT) trial. Sparks DL, Connor DJ, Sabbagh MN, Petersen RB, Lopez J, Browne P ACTA NEUROL SCAND SUPPL 2006 185 3-7
67. Nonsteroidal anti-inflammatory drugs for the prevention of colon cancer. Turner D, Berkel HJ CAN MED ASSOC J 1993 149 5 595-602
68. Gene expression profiling in R-flurbiprofen-treated prostate cancer: R-flurbiprofen regulates prostate stem cell antigen through activation of AKT kinase. Zemskova M, Wechter W, Bashkirova S, Chen CS, Reiter R, Lilly MB. BIOCHEM PHARMACOL 2006 72 10 1257-1267
69. Flurizan™ Alzheimer's disease phase 3 clinical trial (US). Myriad Pharmaceuticals Inc COMPANY WORLD WIDE WEB SITE 2006 December 01
70. Flurizan™ Alzheimer's disease phase 3 clinical trial (global). Myriad Pharmaceuticals Inc COMPANY WORLD WIDE WEB SITE 2006 December 01
71. Flurizan™ prostate cancer clinical trial. Myriad Pharmaceuticals Inc COMPANY WORLD WIDE WEB SITE 2006 December 01
72. R-flurbiprofen in treating patients with localized prostate cancer at risk of recurrence. www.clinicaltrials.gov INTERNET SITE 2002 September 06
73. Global efficacy study of MPC-7869 to treat patients with Alzheimer's. www.clinicaltrials.gov INTERNET SITE 2006 May 02
74. Open-label treatment with MPC-7869 for patients with Alzheimer's who previously participated in an MPC-7869 protocol. www.clinicaltrials.gov INTERNET SITE 2006 September 21
75. Risk of Alzheimer's disease and duration of NSAID use. Stewart WF, Kawas C, Corrada M, Metter EJ NEUROLOGY 1997 48 3 626-632
76. Clinical trials. Halt of Celebrex study threatens drug's future, other trials. Couzin J SCIENCE 2004 306 5705 2170
77. Proapoptotic anti-inflammatory drugs. Myers C, Koki A, Pamukcu R, Wechter W, Padley RJ UROLOGY 2001 57 4 Suppl 1 73-76
78. Flurbiprofen and enantiomers in ophthalmic solution tested as inhibitors of prostanoid synthesis in human blood. van Haeringen NJ, van Sorge AA, van Delft JL, Carballosa Core-Bodelier VM J OCUL PHARMACOL THER 2000 16 4 345-352
79. Nonsteroidal anti-inflammatory drugs repress β-secretase gene promoter activity by the activation of PPARγ. Sastre M, Dewachter I, Rossner S, Bogdanovic N, Rosen E, Borghgraef P, Evert BO, Dumitrescu-Ozimek L, Thal DR, Landreth G, Walter J et al PROC NATL ACAD SCI USA 2006 103 2 443-488
80. A simplified analytical method for a phenotyping cocktail of major CYP450 biotransformation routes. Jerdi MC, Daali Y, Oestreicher MK, Cherkaoui S, Dayer P J PHARM BIOMED ANAL 2004 35 5 1203-1212
81. Stereoselective disposition of flurbiprofen in healthy subjects following administration of the single enantiomers. Geisslinger G, Lotsch J, Menzel S, Kobal G, Brune K BR J CLIN PHARMACOL 1994 37 4 392-394
82. γ-secretase inhibitors for Alzheimer's disease: Balancing efficacy and toxicity. Barten DM, Meredith JE Jr, Zaczek R, Houston JG, Albright CF DRUGS R&D 2006 7 2 87-97
83. Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW J PHARMACOL EXP THER 2002 303 3 1029-1037
84. Chiral chemistry: Traditional methods thrive despite numerous hurdles, including tough luck, slow commercialization of catalytic processes. Rouhi M CHEM ENG NEWS 2004 82 24 47-62
85. Lipase-catalyzed enantioselective esterification of flurbiprofen with n-butanol. Bhandarkar SV, Neau SH ELECTRON J BIOTECHNOL 2000 3 3
86. Pharmacodynamics and pharmacokinetics of the profens: Enantioselectivity, clinical implications, and special reference to S(+)-ibuprofen. Evans AM J CLIN PHARMACOL 1996 36 12 7s-15s
87. Cytokines role in neurodegenerative events. Viviani B, Bartesaghi S, Corsini E, Galli CL, Marinovich M TOXICOL LETT 2004 149 1-3 85-89
88. Induction of apoptosis by R-flurbiprofen in human colon carcinoma cells: Involvement of p53. Grosch S, Schilling K, Janssen A, Maier TJ, Niederberger E, Geisslinger G BIOCHEM PHARMACOL 2005 69 5 831-839
89. The transcriptional activity of the APP intracellular domain-Fe65 complex is inhibited by activation of the NFκB pathway. Zhao Q, Lee FS BIOCHEMISTRY 2003 42 12 3627-34
90. Myriad Genetics announces results of phase 2 prostate cancer trial. Myriad Genetics Inc PRESS RELEASE 2007 January 08