MK-8931- CAS 1286770-55-5

CAS No.: 1286770-55-5

MK-8931 is a BACE1 inhibitor. MK-8931 binds significantly to β-secretase.
target: BACE1.
In vitro:MK-8931 can effectively reduce Aβ40 in cells with a Ki of 7.8 nM and an IC50 of 13 nM. [1] Docking revealed that, with respect to their free binding energy, acylguanidine 7a has the lowest binding energy followed by MK-8931 and pioglitazone and binds significantly to β-secretase. [2]

1:Merck ends trial of potential Alzheimer/’s drug verubecestat. Hawkes N.BMJ. 2017 Feb 15;356:j845. doi: 10.1136/bmj.j845. No abstract available. PMID: 28202490
2:Synthesis of Verubecestat, a BACE1 Inhibitor for the Treatment of Alzheimer/’s Disease. Thaisrivongs DA, Miller SP, Molinaro C, Chen Q, Song ZJ, Tan L, Chen L, Chen W, Lekhal A, Pulicare SK, Xu Y.Org Lett. 2016 Nov 18;18(22):5780-5783. Epub 2016 Nov 4. PMID: 27934506
3:Discovery of the 3-Imino-1,2,4-thiadiazinane 1,1-Dioxide Derivative Verubecestat (MK-8931)-A β-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of Alzheimer/’s Disease. Scott JD, Li SW, Brunskill AP, Chen X, Cox K, Cumming JN, Forman M, Gilbert EJ, Hodgson RA, Hyde LA, Jiang Q, Iserloh U, Kazakevich I, Kuvelkar R, Mei H, Meredith J, Misiaszek J, Orth P, Rossiter LM, Slater M, Stone J, Strickland CO, Voigt JH, Wang G, Wang H, Wu Y, Greenlee WJ, Parker EM, Kennedy ME, Stamford AW.J Med Chem. 2016 Dec 8;59(23):10435-10450. Epub 2016 Nov 18. PMID: 27933948
4:The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer/’s disease patients. 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.Sci Transl Med. 2016 Nov 2;8(363):363ra150. PMID: 27807285