240:
29:
417:
concluded it was unlikely that the drug would show a positive benefit/risk ratio. The final conclusion was that "verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate
Alzheimer’s disease and was associated with treatment-related adverse events". Verubecestat
408:
by June 2017. However, in
February 2017 Merck halted its late-stage trial of verubecestat for mild to moderate Alzheimer's disease after it was reported as having "virtually no chance of finding a positive clinical effect" according to an independent panel of experts. The results of Merck's trial
550:
Kennedy ME, Stamford AW, Chen X, Cox K, Cumming JN, Dockendorf MF, et al. (November 2016). "The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in
Alzheimer's disease patients".
462:
Forman M, Kleijn H, Dockendorf M, Palcza J, Tseng J, Canales C, et al. (2013). "The novel BACE inhibitor MK-8931 dramatically lowers CSF beta-amyloid in patients with mild-to-moderate
Alzheimer's disease".
322:
963:
49:
594:
658:
776:
336:
364:
InChI=1S/C17H17F2N5O3S/c1-17(9-28(26,27)24(2)16(20)23-17)12-7-11(4-5-13(12)19)22-15(25)14-6-3-10(18)8-21-14/h3-8H,9H2,1-2H3,(H2,20,23)(H,22,25)/t17-/m0/s1
418:
was projected to be a breakthrough medicine for dementia related illness, however it is still unknown why the medicine was not effective in humans.
943:
404:
As of
December 2016 it was in two phase 2/3 clinical trials that have progressed to phase 3. EPOCH, was to complete data collection for the
659:"Merck announces EPOCH study of verubecestat for the treatment of people with mild to moderate Alzheimer's disease to stop for lack of efficacy"
439:
595:"Merck presents results of a phase I clinical trial evaluating investigational BACE inhibitor MK-8931 at American Academy of Neurology"
624:
for "Efficacy and safety trial of verubecestat (MK-8931) in participants with prodromal
Alzheimer's disease (MK-8931-019) (APECS)" at
769:
356:
94:
70:
696:
for "Efficacy and Safety Trial of
Verubecestat (MK-8931) in Participants With Prodromal Alzheimer's Disease (MK-8931-019)" at
802:
598:
645:
for "An efficacy and safety trial of verubecestat (MK-8931) in mild to moderate
Alzheimer's disease (P07738) (EPOCH)" at
762:
179:
413:(early stage) Alzheimer's were expected in February 2019. However, the trial was terminated in February 2018, after a
219:
754:
958:
414:
387:
953:
948:
235:
891:
820:
444:
114:
697:
646:
625:
576:
480:
401:
In April 2012 phase I clinical results were announced. Phase 1b results have also been reported.
740:
568:
532:
168:
674:"Merck & Co. terminates Phase III study of verubecestat in prodromal Alzheimer's disease"
123:
730:
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472:
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937:
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872:
709:
Egan MF, Kost J, Tariot PN, Aisen PS, Cummings JL, Vellas B, et al. (May 2018).
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298:
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20:
887:
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410:
744:
711:"Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer's Disease"
572:
536:
726:
28:
789:
841:
134:
208:
321:
312:
503:"Targeting the β secretase BACE1 for Alzheimer's disease therapy"
908:
661:(Press release). Merck Sharp & Dohme Corp. 14 February 2017.
199:
758:
440:"New Alzheimer's drug clears milestone in human clinical trial"
398:(BACE1), which, after initial promise proved disappointing.
224:
597:. Merck Sharp & Dohme Corp. April 2012. Archived from
344:
C1(CS(=O)(=O)N(C(=N1)N)C)c2cc(ccc2F)NC(=O)c3ccc(cn3)F
906:
850:
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113:
105:-{3--4-fluorophenyl}-5-fluoropyridine-2-carboxamide
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48:
40:
35:
386:) was an experimental drug for the treatment of
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8:
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19:
964:Experimental drugs for Alzheimer's disease
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27:
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715:The New England Journal of Medicine
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14:
409:of verubecestat on patients with
279:
273:
267:
883:Meclofenoxate (centrophenoxine)
369:Key:YHYKUSGACIYRML-KRWDZBQOSA-N
944:Drugs not assigned an ATC code
553:Science Translational Medicine
501:Yan R, Vassar R (March 2014).
291:
285:
261:
1:
672:Barber J (13 February 2018).
519:10.1016/S1474-4422(13)70276-X
565:10.1126/scitranslmed.aad9704
438:Makin S (2 November 2016).
980:
477:10.1016/j.jalz.2013.04.083
465:Alzheimer's & Dementia
251:Chemical and physical data
415:data monitoring committee
352:
332:
90:
26:
406:primary outcome measure
690:Clinical trial number
639:Clinical trial number
618:Clinical trial number
727:10.1056/NEJMoa1706441
507:The Lancet. Neurology
445:Scientific American
388:Alzheimer's disease
23:
698:ClinicalTrials.gov
647:ClinicalTrials.gov
626:ClinicalTrials.gov
959:Enzyme inhibitors
931:
930:
851:Other medications
792:agents (ATC code
721:(18): 1691–1703.
559:(363): 363ra150.
377:
376:
323:Interactive image
220:CompTox Dashboard
16:Chemical compound
971:
786:Psychoanaleptics
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772:
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678:FirstWord Pharma
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396:beta-secretase 1
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812:Benzgalantamine
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78:Investigational
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803:AChE inhibitor
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513:(3): 319–329.
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907:Experimental
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873:Ginkgo folium
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36:Clinical data
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954:Carboxamides
949:Fluoroarenes
923:Verubecestat
922:
918:Lanabecestat
837:Rivastigmine
718:
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619:
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603:. Retrieved
599:the original
589:
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468:
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443:
403:
400:
390:. It is an
383:
380:Verubecestat
379:
378:
124:1286770-55-5
102:
71:Legal status
65:Legal status
21:Verubecestat
898:Nicergoline
827:Galantamine
805:medications
796:and others)
693:NCT01953601
642:NCT01739348
621:NCT01953601
471:(4): P139.
306: g·mol
86:Identifiers
41:Other names
938:Categories
911:inhibitors
892:+donepezil
863:Bifemelane
858:Aducanumab
832:Ipidacrine
821:+memantine
605:2012-07-16
422:References
311:3D model (
299:Molar mass
189:J1I0P6WT7T
160:ChemSpider
115:CAS Number
95:IUPAC name
888:Memantine
878:Lecanemab
868:Donanemab
817:Donepezil
411:prodromal
392:inhibitor
790:dementia
745:29719179
573:27807285
537:24556009
485:54387517
169:31399364
149:51352361
50:ATC code
842:Tacrine
788:: Anti-
736:6776074
581:4579605
528:4086426
384:MK-8931
257:Formula
135:PubChem
44:MK-8931
743:
733:
579:
571:
535:
525:
483:
337:SMILES
304:409.41
209:D10739
577:S2CID
481:S2CID
357:InChI
313:JSmol
909:BACE
794:N06D
741:PMID
569:PMID
533:PMID
200:KEGG
180:UNII
57:None
731:PMC
723:doi
719:378
561:doi
523:PMC
515:doi
473:doi
394:of
225:EPA
139:CID
940::
739:.
729:.
717:.
713:.
676:.
632:^
575:.
567:.
555:.
531:.
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511:13
509:.
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493:^
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442:.
430:^
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890:(
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819:(
778:e
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382:(
315:)
292:S
289:3
286:O
283:5
280:N
277:2
274:F
268:H
262:C
227:)
223:(
103:N
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
