MK-8719
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MedKoo CAT#: 555640

CAS#: 1382799-40-7

Description: MK-8719 is a highly potent and selective OGA inhibitor (EC50 = 52.7 nM) which is a Potential Treatment for Tauopathies. MK-8719 showed excellent CNS penetration that has been advanced to first-in-human phase I clinical trials.

Chemical Structure

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MK-8719
CAS# 1382799-40-7
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 555640
Name: MK-8719
CAS#: 1382799-40-7
Chemical Formula: C9H14F2N2O3S
Exact Mass: 268.07
Molecular Weight: 268.279
Elemental Analysis: C, 40.29; H, 5.26; F, 14.16; N, 10.44; O, 17.89; S, 11.95

Price and Availability

Size Price Availability Quantity
10mg USD 450 2 Weeks
25mg USD 750 2 Weeks
50mg USD 1250 2 Weeks
100mg USD 1950 2 Weeks
200mg USD 2950 2 Weeks
500mg USD 4950 2 Weeks
1g USD 6450 2 Weeks
2g USD 9850 2 Weeks
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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

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: >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.

Product Data:
Product Data
Instruction:
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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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 63.5 236.69
Ethanol 54.0 201.28
Water 10.3 38.52

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.

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: 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.

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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.