Verubecestat free base
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MedKoo CAT#: 330124

CAS#: 1286770-55-5 (free base)

Description: Verubecestat, also known as MK-8931 or SCH 900931, is a potent and selective beta-secretase inhibitor, and BACE1 protein inhibitor or Beta-site APP-cleaving enzyme 1 inhibitor. Verubecestat is a promising novel therapeutic drug candidate in Alzheimer's disease. Verubecestat reduced Aβ cerebral spinal fluids (CSF) levels up to 92% and was well tolerated by patients.

Chemical Structure

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Verubecestat free base
CAS# 1286770-55-5 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 330124
Name: Verubecestat free base
CAS#: 1286770-55-5 (free base)
Chemical Formula: C17H17F2N5O3S
Exact Mass: 409.10
Molecular Weight: 409.410
Elemental Analysis: C, 49.87; H, 4.19; F, 9.28; N, 17.11; O, 11.72; S, 7.83

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 700 Ready to ship
200mg USD 1350 Ready to ship
500mg USD 2650 Ready to ship
1g USD 4250 Ready to ship
2g USD 6650 Ready to ship
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Related CAS #: 2095432-65-6 (TFA)   1286770-55-5 (free base)   1875153-95-9 (Tosylate)   1970144-54-7 (HBr)   1897370-45-4 (hydrate),  

Synonym: MK-8931; MK 8931; MK8931; MK-8931-009; SCH 900931; SCH-900931; SCH900931; Verubecestat free base,

IUPAC/Chemical Name: (R)-N-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-5-fluoropicolinamide

InChi Key: YHYKUSGACIYRML-KRWDZBQOSA-N

InChi Code: 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

SMILES Code: O=C(NC1=CC=C(F)C([C@@](C2)(C)N=C(N)N(C)S2(=O)=O)=C1)C3=NC=C(F)C=C3

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: Verubecestat (MK-8931) is a BACE1 and BACE2 inhibitor with Ki values of 2.2 nM and 0.38 nM.
In vitro activity: TBD
In vivo activity: Verubecestat (MK-8931) is a potent, selective, structurally unique BACE1 inhibitor that reduced plasma, cerebrospinal fluid (CSF), and brain concentrations of Aβ40, Aβ42, and sAPPβ (a direct product of BACE1 enzymatic activity) after acute and chronic administration to rats and monkeys. Reference: Sci Transl Med. 2016 Nov 2;8(363):363ra150. https://stm.sciencemag.org/content/8/363/363ra150.short

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 50.7 123.76
Ethanol 11.0 26.87

Preparing Stock Solutions

The following data is based on the product molecular weight 409.41 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. 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. The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer's disease patients. Sci Transl Med. 2016 Nov 2;8(363):363ra150. doi: 10.1126/scitranslmed.aad9704. PMID: 27807285.
In vitro protocol: TBD
In vivo protocol: 1. 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. The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer's disease patients. Sci Transl Med. 2016 Nov 2;8(363):363ra150. doi: 10.1126/scitranslmed.aad9704. PMID: 27807285.

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1: Thaisrivongs DA, Morris WJ, Tan L, Song ZJ, Lyons TW, Waldman JH, Naber JR, Chen W, Chen L, Zhang B, Yang J. A Next Generation Synthesis of BACE1 Inhibitor Verubecestat (MK-8931). Org Lett. 2018 Mar 16;20(6):1568-1571. doi: 10.1021/acs.orglett.8b00259. Epub 2018 Feb 26. PubMed PMID: 29481097.

2: Chen W, Meng D, N'Zemba B, Morris WJ. Palladium-Catalyzed Enantioselective Synthesis of Cyclic Sulfamidates and Application to a Synthesis of Verubecestat. Org Lett. 2018 Mar 2;20(5):1265-1268. doi: 10.1021/acs.orglett.7b03639. Epub 2018 Feb 20. PubMed PMID: 29461065.

3: Barhate CL, Lopez DA, Makarov AA, Bu X, Morris WJ, Lekhal A, Hartman R, Armstrong DW, Regalado EL. Macrocyclic glycopeptide chiral selectors bonded to core-shell particles enables enantiopurity analysis of the entire verubecestat synthetic route. J Chromatogr A. 2018 Mar 2;1539:87-92. doi: 10.1016/j.chroma.2018.01.042. Epub 2018 Jan 31. PubMed PMID: 29397980.

4: Geerts H, Spiros A, Roberts P. Impact of amyloid-beta changes on cognitive outcomes in Alzheimer's disease: analysis of clinical trials using a quantitative systems pharmacology model. Alzheimers Res Ther. 2018 Feb 2;10(1):14. doi: 10.1186/s13195-018-0343-5. PubMed PMID: 29394903; PubMed Central PMCID: PMC5797372.

5: Villarreal S, Zhao F, Hyde LA, Holder D, Forest T, Sondey M, Chen X, Sur C, Parker EM, Kennedy ME. Chronic Verubecestat Treatment Suppresses Amyloid Accumulation in Advanced Aged Tg2576-AβPPswe Mice Without Inducing Microhemorrhage. J Alzheimers Dis. 2017;59(4):1393-1413. doi: 10.3233/JAD-170056. PubMed PMID: 28800329; PubMed Central PMCID: PMC5611839.

6: Prati F, Bottegoni G, Bolognesi ML, Cavalli A. BACE-1 Inhibitors: From Recent Single-Target Molecules to Multitarget Compounds for Alzheimer's Disease. J Med Chem. 2018 Feb 8;61(3):619-637. doi: 10.1021/acs.jmedchem.7b00393. Epub 2017 Aug 8. PubMed PMID: 28749667.

7: Hung SY, Fu WM. Drug candidates in clinical trials for Alzheimer's disease. J Biomed Sci. 2017 Jul 19;24(1):47. doi: 10.1186/s12929-017-0355-7. Review. PubMed PMID: 28720101; PubMed Central PMCID: PMC5516350.

8: Mullard A. BACE inhibitor bust in Alzheimer trial. Nat Rev Drug Discov. 2017 Mar 1;16(3):155. doi: 10.1038/nrd.2017.43. PubMed PMID: 28248932.

9: Hawkes N. Merck ends trial of potential Alzheimer's drug verubecestat. BMJ. 2017 Feb 15;356:j845. doi: 10.1136/bmj.j845. PubMed PMID: 28202490.

10: Thaisrivongs DA, Miller SP, Molinaro C, Chen Q, Song ZJ, Tan L, Chen L, Chen W, Lekhal A, Pulicare SK, Xu Y. Synthesis of Verubecestat, a BACE1 Inhibitor for the Treatment of Alzheimer's Disease. Org Lett. 2016 Nov 18;18(22):5780-5783. Epub 2016 Nov 4. PubMed PMID: 27934506.

11: 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. 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. J Med Chem. 2016 Dec 8;59(23):10435-10450. Epub 2016 Nov 18. PubMed PMID: 27933948.

12: 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. The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer's disease patients. Sci Transl Med. 2016 Nov 2;8(363):363ra150. PubMed PMID: 27807285.

13: Panza F, Seripa D, Solfrizzi V, Imbimbo BP, Lozupone M, Leo A, Sardone R, Gagliardi G, Lofano L, Creanza BC, Bisceglia P, Daniele A, Bellomo A, Greco A, Logroscino G. Emerging drugs to reduce abnormal β-amyloid protein in Alzheimer's disease patients. Expert Opin Emerg Drugs. 2016 Dec;21(4):377-391. Epub 2016 Oct 6. Review. PubMed PMID: 27678025.

14: Yan R. Stepping closer to treating Alzheimer's disease patients with BACE1 inhibitor drugs. Transl Neurodegener. 2016 Jul 14;5:13. doi: 10.1186/s40035-016-0061-5. eCollection 2016. Review. PubMed PMID: 27418961; PubMed Central PMCID: PMC4944430.

15: Evin G. Future Therapeutics in Alzheimer's Disease: Development Status of BACE Inhibitors. BioDrugs. 2016 Jun;30(3):173-94. doi: 10.1007/s40259-016-0168-3. Review. PubMed PMID: 27023706.

Zhai, K., Huang, Z., Huang, Q. et al. Pharmacological inhibition of BACE1 suppresses glioblastoma growth by stimulating macrophage phagocytosis of tumor cells. Nat Cancer 2, 1136–1151 (2021). https://doi.org/10.1038/s43018-021-00267-9