Verubecestat Explained
| Iupac Name: | N--5-fluoropyridine-2-carboxamide |
| Legal Status: | Investigational |
| Cas Number: | 1286770-55-5 |
| Atc Prefix: | None |
| Chemspiderid: | 31399364 |
| Kegg: | D10739 |
| Pubchem: | 51352361 |
| Unii: | J1I0P6WT7T |
| Synonyms: | MK-8931 |
| C: | 17 |
| H: | 17 |
| F: | 2 |
| N: | 5 |
| O: | 3 |
| S: | 1 |
| Smiles: | C[C@]1(CS(=O)(=O)N(C(=N1)N)C)c2cc(ccc2F)NC(=O)c3ccc(cn3)F |
| Stdinchi: | 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 |
| Stdinchikey: | YHYKUSGACIYRML-KRWDZBQOSA-N |
Verubecestat (MK-8931) was an experimental drug for the treatment of Alzheimer's disease.[1] It is an inhibitor of beta-secretase 1 (BACE1),[2] [3] [4] which, after initial promise proved disappointing.
In April 2012 phase I clinical results were announced.[5] Phase 1b results have also been reported.[3] [2]
it was in two phase 2/3 clinical trials that have progressed to phase 3.[1] EPOCH, was to complete data collection for the primary outcome measure 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.[6] The results of Merck's trial of verubecestat on patients with prodromal (early stage) Alzheimer's were expected in February 2019. However, the trial was terminated in February 2018, after a data monitoring committee concluded it was unlikely that the drug would show a positive benefit/risk ratio.[7] 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 was projected to be a breakthrough medicine for dementia related illness, however it is still unknown why the medicine was not effective in humans. [8]
Notes and References
- New Alzheimer's drug clears milestone in human clinical trial . Makin S . 2 November 2016 . Scientific American.
- 10.1016/j.jalz.2013.04.083. The novel BACE inhibitor MK-8931 dramatically lowers CSF beta-amyloid in patients with mild-to-moderate Alzheimer's disease. Alzheimer's & Dementia. 9. 4. P139. 2013. Forman M, Kleijn H, Dockendorf M, Palcza J, Tseng J, Canales C, Egan M, Kennedy M, Laterza O, Ma L, Scott J, Tanen M, Apter J, Backonja M, Ereshefsky L, Gevorkyan H, Jhee S, Rynders R, Zari A, Bryan E, Wagner J, Troyer M, Stone J . 54387517. 6 .
- Yan R, Vassar R . Targeting the β secretase BACE1 for Alzheimer's disease therapy . The Lancet. Neurology . 13 . 3 . 319–329 . March 2014 . 24556009 . 4086426 . 10.1016/S1474-4422(13)70276-X .
- Kennedy ME, Stamford AW, Chen X, Cox K, Cumming JN, Dockendorf MF, Egan M, Ereshefsky L, Hodgson RA, Hyde LA, Jhee S, Kleijn HJ, Kuvelkar R, Li W, Mattson BA, Mei H, Palcza J, Scott JD, Tanen M, Troyer MD, Tseng JL, Stone JA, Parker EM, Forman MS . 6 . The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer's disease patients . Science Translational Medicine . 8 . 363 . 363ra150 . November 2016 . 27807285 . 10.1126/scitranslmed.aad9704 . 4579605 .
- News: Merck presents results of a phase I clinical trial evaluating investigational BACE inhibitor MK-8931 at American Academy of Neurology . April 2012 . 2012-07-16 . https://web.archive.org/web/20120728084446/http://www.merck.com/newsroom/news-release-archive/research-and-development/2012_0427.html . 2012-07-28 . dead . Merck Sharp & Dohme Corp. .
- Merck announces EPOCH study of verubecestat for the treatment of people with mild to moderate Alzheimer's disease to stop for lack of efficacy . 14 February 2017 . Merck Sharp & Dohme Corp. .
- Web site: Barber J . 13 February 2018 . Merck & Co. terminates Phase III study of verubecestat in prodromal Alzheimer's disease. . FirstWord Pharma .
- Egan MF, Kost J, Tariot PN, Aisen PS, Cummings JL, Vellas B, Sur C, Mukai Y, Voss T, Furtek C, Mahoney E, Harper Mozley L, Vandenberghe R, Mo Y, Michelson D . 6 . Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer's Disease . The New England Journal of Medicine . 378 . 18 . 1691–1703 . May 2018 . 29719179 . 6776074 . 10.1056/NEJMoa1706441 .
