Verubecestat free base | CAS#1286770-55-5 | BACE1 inhibitor

MedKoo Cat#: 330124 | Name: Verubecestat free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

Verubecestat free base

CAS#1286770-55-5 (free base)

Theoretical Analysis

MedKoo Cat#: 330124

Name: Verubecestat free base

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

Chemical Formula: C17H17F2N5O3S

Exact Mass: 409.1020

Molecular Weight: 409.41

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
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,650.00	Ready to ship
1g	USD 2,950.00	Ready to ship
2g	USD 5,250.00	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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot# A9T11K11

View CoA: current batch, Lot#A9T12K06

QC Data

View QC data: current batch, Lot# A9T11K11

View QC data: current batch, Lot#A9T12K06

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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

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

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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: Tosat-Bitrián C, Bueso de Barrio JA, Stewart MH, Susumu K, Medintz IL, Díaz SA, Palomo V. Membrane-Targeted Quantum Dot-Based BACE1 Activity Sensors for In Vitro and In Cellulo Assays. ACS Appl Mater Interfaces. 2024 Nov 20;16(46):63186-63194. doi: 10.1021/acsami.4c12560. Epub 2024 Nov 8. PMID: 39515812; PMCID: PMC11583121. 2: Volloch V, Rits-Volloch S. Principles of Design of Clinical Trials for Prevention and Treatment of Alzheimer's Disease and Aging-Associated Cognitive Decline in the ACH2.0 Perspective: Potential Outcomes, Challenges, and Solutions. J Alzheimers Dis Rep. 2023 Aug 28;7(1):921-955. doi: 10.3233/ADR-230037. PMID: 37849639; PMCID: PMC10578334. 3: Xu E, Park S, Calderon J, Cao D, Liang B. In Silico Identification and In Vitro Validation of Repurposed Compounds Targeting the RSV Polymerase. Microorganisms. 2023 Jun 18;11(6):1608. doi: 10.3390/microorganisms11061608. PMID: 37375110; PMCID: PMC10302583. 4: Galeana-Ascencio RA, Mendieta L, Limon DI, Gnecco D, Terán JL, Orea ML, Carrasco-Carballo A. β-Secretase-1: In Silico Drug Reposition for Alzheimer's Disease. Int J Mol Sci. 2023 May 3;24(9):8164. doi: 10.3390/ijms24098164. PMID: 37175873; PMCID: PMC10179340. 5: Voss T, Kost J, Mercer SP, Furtek C, Randolph C, Lines C, Egan MF, Cummings JL. Progression from Prodromal Alzheimer's Disease to Mild Alzheimer's Disease Dementia in the Verubecestat APECS Study: Adjudicating Diagnostic Transitions. J Alzheimers Dis. 2023;92(1):341-348. doi: 10.3233/JAD-220836. PMID: 36744336; PMCID: PMC10023445. 6: Li H, Wang YJ, Geng XN, Kang YR, Wang YL, Qiu XJ. Pharmacokinetics of Herb- Drug Interactions of Plumbagin and Tazemetostat in Rats by UPLC-MS/MS. Drug Des Devel Ther. 2022 Sep 29;16:3385-3394. doi: 10.2147/DDDT.S384156. PMID: 36199632; PMCID: PMC9529013. 7: Oddens BJ, Agaku IT, Snyder ES, Malbecq W, Wang WW, Kaplan KM, Koch GG, Rockhold FW. Exploratory analyses of clinical trial data used for health technology assessments: a retrospective evaluation. BMJ Open. 2022 Jul 29;12(7):e058146. doi: 10.1136/bmjopen-2021-058146. PMID: 35906049; PMCID: PMC9345082. 8: Oblak AL, Cope ZA, Quinney SK, Pandey RS, Biesdorf C, Masters AR, Onos KD, Haynes L, Keezer KJ, Meyer JA, Peters JS, Persohn SA, Bedwell AA, Eldridge K, Speedy R, Little G, Williams SP, Noarbe B, Obenaus A, Sasner M, Howell GR, Carter GW, Williams H, Lamb BT, Territo PR, Sukoff Rizzo SJ. Prophylactic evaluation of verubecestat on disease- and symptom-modifying effects in 5XFAD mice. Alzheimers Dement (N Y). 2022 Jul 14;8(1):e12317. doi: 10.1002/trc2.12317. PMID: 35846156; PMCID: PMC9281365. 9: Sur C, Adamczuk K, Scott D, Kost J, Sampat M, Buckley C, Farrar G, Newton B, Suhy J, Bennacef I, Egan MF. Evaluation of 18F-flutemetamol amyloid PET image analysis parameters on the effect of verubecestat on brain amlyoid load in Alzheimer's disease. Mol Imaging Biol. 2022 Dec;24(6):862-873. doi: 10.1007/s11307-022-01735-z. Epub 2022 Jul 7. PMID: 35794343. 10: Watamura N, Sato K, Shiihashi G, Iwasaki A, Kamano N, Takahashi M, Sekiguchi M, Mihira N, Fujioka R, Nagata K, Hashimoto S, Saito T, Ohshima T, Saido TC, Sasaguri H. An isogenic panel of App knock-in mouse models: Profiling β-secretase inhibition and endosomal abnormalities. Sci Adv. 2022 Jun 10;8(23):eabm6155. doi: 10.1126/sciadv.abm6155. Epub 2022 Jun 8. PMID: 35675411; PMCID: PMC9177067. 11: Anderson M, Dockendorf MF, McIntosh I, Xie I, Breidinger S, Meng D, Ren S, Zhong W, Zhang L, Roadcap B, Bateman KP, Stone J, Woolf E. An Investigation of Instability in Dried Blood Spot Samples for Pharmacokinetic Sampling in Phase 3 Trials of Verubecestat. AAPS J. 2022 Apr 6;24(3):52. doi: 10.1208/s12248-022-00683-4. PMID: 35384529. 12: Dockendorf MF, Jaworowicz D, Humphrey R, Anderson M, Breidinger S, Ma L, Taylor T, Dupre N, Jones C, Furtek C, Kantesaria B, Bateman KP, Woolf E, Egan MF, Stone JA. A Model-Based Approach to Bridging Plasma and Dried Blood Spot Concentration Data for Phase 3 Verubecestat Trials. AAPS J. 2022 Apr 6;24(3):53. doi: 10.1208/s12248-022-00682-5. PMID: 35384522. 13: Patel S, Bansoad AV, Singh R, Khatik GL. BACE1: A Key Regulator in Alzheimer's Disease Progression and Current Development of its Inhibitors. Curr Neuropharmacol. 2022;20(6):1174-1193. doi: 10.2174/1570159X19666211201094031. PMID: 34852746; PMCID: PMC9886827. 14: Querol-Vilaseca M, Sirisi S, Molina-Porcel L, Molina B, Pegueroles J, Ferrer-Raventós P, Nuñez-Llaves R, Dols-Icardo O, Balasa M, Iulita MF, Blesa R, Belbin O, Clarimon J, Fortea J, Gelpi E, Sánchez-Valle R, Lleó A. Neuropathology of a patient with Alzheimer disease treated with low doses of verubecestat. Neuropathol Appl Neurobiol. 2022 Apr;48(3):e12781. doi: 10.1111/nan.12781. Epub 2021 Dec 7. PMID: 34825396. 15: Das B, Singh N, Yao AY, Zhou J, He W, Hu X, Yan R. BACE1 controls synaptic function through modulating release of synaptic vesicles. Mol Psychiatry. 2021 Nov;26(11):6394-6410. doi: 10.1038/s41380-021-01166-2. Epub 2021 Jun 22. PMID: 34158621; PMCID: PMC8760050. 16: Madrasi K, Das R, Mohmmadabdul H, Lin L, Hyman BT, Lauffenburger DA, Albers MW, Rissman RA, Burke JM, Apgar JF, Wille L, Gruenbaum L, Hua F. Systematic in silico analysis of clinically tested drugs for reducing amyloid-beta plaque accumulation in Alzheimer's disease. Alzheimers Dement. 2021 Sep;17(9):1487-1498. doi: 10.1002/alz.12312. Epub 2021 May 2. PMID: 33938131; PMCID: PMC8478725. 17: Qu L, Ji L, Wang C, Luo H, Li S, Peng W, Yin F, Lu D, Liu X, Kong L, Wang X. Synthesis and evaluation of multi-target-directed ligands with BACE-1 inhibitory and Nrf2 agonist activities as potential agents against Alzheimer's disease. Eur J Med Chem. 2021 Jul 5;219:113441. doi: 10.1016/j.ejmech.2021.113441. Epub 2021 Apr 7. PMID: 33862517. 18: Miranda A, Montiel E, Ulrich H, Paz C. Selective Secretase Targeting for Alzheimer's Disease Therapy. J Alzheimers Dis. 2021;81(1):1-17. doi: 10.3233/JAD-201027. PMID: 33749645. 19: Fujimoto K, Yoshida S, Tadano G, Asada N, Fuchino K, Suzuki S, Matsuoka E, Yamamoto T, Yamamoto S, Ando S, Kanegawa N, Tonomura Y, Ito H, Moechars D, Rombouts FJR, Gijsen HJM, Kusakabe KI. Structure-Based Approaches to Improving Selectivity through Utilizing Explicit Water Molecules: Discovery of Selective β-Secretase (BACE1) Inhibitors over BACE2. J Med Chem. 2021 Mar 25;64(6):3075-3085. doi: 10.1021/acs.jmedchem.0c01858. Epub 2021 Mar 15. PMID: 33719429. 20: Chambers M, Delport A, Hewer R. The use of the cellular thermal shift assay for the detection of intracellular beta-site amyloid precursor protein cleaving enzyme-1 ligand binding. Mol Biol Rep. 2021 Mar;48(3):2957-2962. doi: 10.1007/s11033-021-06229-9. Epub 2021 Mar 4. PMID: 33665787.

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