Synonym
MK-8719; MK 8719; MK8719;
IUPAC/Chemical Name
(3aR,5S,6S,7R,7aR)-5-(difluoromethyl)-2-(ethylamino)-3a,6,7,7a-tetrahydro-5H-pyrano[3,2-d]thiazole-6,7-diol
InChi Key
UDQTXCHQKHIQMH-KYGLGHNPSA-N
InChi Code
InChI=1S/C9H14F2N2O3S/c1-2-12-9-13-3-4(14)5(15)6(7(10)11)16-8(3)17-9/h3-8,14-15H,2H2,1H3,(H,12,13)/t3-,4-,5+,6+,8-/m1/s1
SMILES Code
O[C@H]1[C@H](O)[C@@]2([H])N=C(NCC)S[C@@]2([H])O[C@@H]1C(F)F
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
>3 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
Inhibition of O-GlcNAcase (OGA) has emerged as a promising therapeutic approach to treat tau pathology in neurodegenerative diseases such as Alzheimer’s disease and progressive supranuclear palsy. Beginning with carbohydrate-based lead molecules, we pursued an optimization strategy of reducing polar surface area to align the desired drug-like properties of potency, selectivity, high central nervous system (CNS) exposure, metabolic stability, favorable pharmacokinetics, and robust in vivo pharmacodynamic response.
Biological target:
MK-8719 is a highly potent and selective O-GlcNAcase (OGA) inhibitor (Ki=7.9 nM for hOGA).
In vitro activity:
In vitro, MK-8719 is a potent inhibitor of the human OGA enzyme with comparable activity against the corresponding enzymes from mouse, rat, and dog.
Reference: J Pharmacol Exp Ther. 2020 Aug;374(2):252-263. https://pubmed.ncbi.nlm.nih.gov/32493725/
In vivo activity:
In vivo, oral administration of MK-8719 elevates brain and peripheral blood mononuclear cell O-GlcNAc levels in a dose-dependent manner. In addition, positron emission tomography imaging studies demonstrate robust target engagement of MK-8719 in the brains of rats and rTg4510 mice. In the rTg4510 mouse model of human tauopathy, MK-8719 significantly increases brain O-GlcNAc levels and reduces pathologic tau.
Reference: J Pharmacol Exp Ther. 2020 Aug;374(2):252-263. https://pubmed.ncbi.nlm.nih.gov/32493725/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
63.5 |
236.69 |
|
| Ethanol |
54.0 |
201.28 |
|
| Water |
10.3 |
38.52 |
|
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
268.28
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:
Wang X, Li W, Marcus J, Pearson M, Song L, Smith K, Terracina G, Lee J, Hong KK, Lu SX, Hyde L, Chen SC, Kinsley D, Melchor JP, Rubins DJ, Meng X, Hostetler E, Sur C, Zhang L, Schachter JB, Hess JF, Selnick HG, Vocadlo DJ, McEachern EJ, Uslaner JM, Duffy JL, Smith SM. MK-8719, a Novel and Selective O-GlcNAcase Inhibitor That Reduces the Formation of Pathological Tau and Ameliorates Neurodegeneration in a Mouse Model of Tauopathy. J Pharmacol Exp Ther. 2020 Aug;374(2):252-263. doi: 10.1124/jpet.120.266122. Epub 2020 Jun 3. PMID: 32493725.
In vitro protocol:
Wang X, Li W, Marcus J, Pearson M, Song L, Smith K, Terracina G, Lee J, Hong KK, Lu SX, Hyde L, Chen SC, Kinsley D, Melchor JP, Rubins DJ, Meng X, Hostetler E, Sur C, Zhang L, Schachter JB, Hess JF, Selnick HG, Vocadlo DJ, McEachern EJ, Uslaner JM, Duffy JL, Smith SM. MK-8719, a Novel and Selective O-GlcNAcase Inhibitor That Reduces the Formation of Pathological Tau and Ameliorates Neurodegeneration in a Mouse Model of Tauopathy. J Pharmacol Exp Ther. 2020 Aug;374(2):252-263. doi: 10.1124/jpet.120.266122. Epub 2020 Jun 3. PMID: 32493725.
In vivo protocol:
Wang X, Li W, Marcus J, Pearson M, Song L, Smith K, Terracina G, Lee J, Hong KK, Lu SX, Hyde L, Chen SC, Kinsley D, Melchor JP, Rubins DJ, Meng X, Hostetler E, Sur C, Zhang L, Schachter JB, Hess JF, Selnick HG, Vocadlo DJ, McEachern EJ, Uslaner JM, Duffy JL, Smith SM. MK-8719, a Novel and Selective O-GlcNAcase Inhibitor That Reduces the Formation of Pathological Tau and Ameliorates Neurodegeneration in a Mouse Model of Tauopathy. J Pharmacol Exp Ther. 2020 Aug;374(2):252-263. doi: 10.1124/jpet.120.266122. Epub 2020 Jun 3. PMID: 32493725.
1: Selnick H, Hess JF, Tang C, Liu K, Schachter J, Ballard JE, Marcus JN, Klein
DJ, Wang X, Pearson M, Savage MJ, Kaul R, Li T, Vocadlo DJ, Zhou Y, Zhu Y, Mu C,
Wang Y, Wei Z, Bai C, Duffy JL, McEachern EJ. Discovery of MK-8719, A Potent
O-GlcNAcase Inhibitor as a Potential Treatment for Tauopathies. J Med Chem. 2019
Sep 5. doi: 10.1021/acs.jmedchem.9b01090. [Epub ahead of print] PubMed PMID:
31487175.
