MK-0941 mesylate, the mesylate salt of MK0941, is a novel, orally bioactive and allosteric glucokinase activator (GKA) with anti-diabetic effects. It activates glucokinase with EC50s of 240 and 65 nM for recombinant human glucokinase in the presence of 2.5 and 10 mM glucose, respectively. It has the potential to be used for the treatment of type 2 diabetes. MK-0941 led to improvements in glycemic control that were not sustained. MK-0941 was associated with an increased incidence of hypoglycemia and elevations in triglycerides and blood.

Physicochemical Properties

Molecular Formula	C22H28N4O9S2
Molecular Weight	556.60912322998
Exact Mass	556.13
CAS #	1137916-97-2
Related CAS #	MK-0941 free base;752240-01-0
PubChem CID	25235800
Appearance	Light yellow to yellow solid powder
LogP	4.151
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	9
Heavy Atom Count	37
Complexity	810
Defined Atom Stereocenter Count	1
SMILES	CCS(=O)(=O)C1=NC=C(C=C1)OC2=CC(=CC(=C2)C(=O)NC3=NN(C=C3)C)O[C@@H](C)CO.CS(=O)(=O)O
InChi Key	PIDNRTWDGDJKSQ-UQKRIMTDSA-N
InChi Code	InChI=1S/C21H24N4O6S.CH4O3S/c1-4-32(28,29)20-6-5-16(12-22-20)31-18-10-15(9-17(11-18)30-14(2)13-26)21(27)23-19-7-8-25(3)24-191-5(2,3)4/h5-12,14,26H,4,13H2,1-3H3,(H,23,24,27)1H3,(H,2,3,4)/t14-/m0./s1
Chemical Name	3-((6-(ethylsulfonyl)-3-pyridinyl)oxy)-5-((1S)-2-hydroxy-1-methylethoxy)-N-(1-methyl-1H-pyrazol-3-yl)benzamide mesylate
Synonyms	MK-0941 MK 0941 MK0941 MK-0941 mesylate.
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

References

[1]Pharmacokinetic and pharmacodynamic properties of the glucokinase activator MK-0941 in rodent models of type 2 diabetes and healthy dogs. Mol Pharmacol. 2011 Dec;80(6):1156-65 [2] Comparison of Deconvolution-Based and Absorption Modeling IVIVC for Extended Release Formulations of a BCS III Drug Development Candidate. AAPS J. 2015 Nov;17(6):1492-500.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~179.66 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.17 mg/mL (3.90 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.17 mg/mL (3.90 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.17 mg/mL (3.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.7966 mL	8.9830 mL	17.9659 mL
	5 mM	0.3593 mL	1.7966 mL	3.5932 mL
	10 mM	0.1797 mL	0.8983 mL	1.7966 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.