AR453588 is a potent orally bioavailable anti-diabetic glucokinase activator with EC50 of 42 nM. AR453588 has hypoglycemic effects.

Physicochemical Properties

Molecular Formula	C25H25N7O2S2
Molecular Weight	519.6417
Exact Mass	519.151
CAS #	1065609-00-8
Related CAS #	AR453588 hydrochloride;1065606-97-4
PubChem CID	59291641
Appearance	Off-white to light yellow solid powder
LogP	4.2
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	7
Heavy Atom Count	36
Complexity	714
Defined Atom Stereocenter Count	0
SMILES	S1C(N([H])C2=C(C([H])=C(C([H])=N2)SC2=C([H])C([H])=C([H])C([H])=N2)OC2C([H])=C([H])C([H])=NC=2C([H])([H])[H])=NC(C2([H])C([H])([H])C([H])([H])N(C(C([H])([H])[H])=O)C([H])([H])C2([H])[H])=N1
InChi Key	WITGITFYEMHCEZ-UHFFFAOYSA-N
InChi Code	InChI=1S/C25H25N7O2S2/c1-16-20(6-5-11-26-16)34-21-14-19(35-22-7-3-4-10-27-22)15-28-24(21)30-25-29-23(31-36-25)18-8-12-32(13-9-18)17(2)33/h3-7,10-11,14-15,18H,8-9,12-13H2,1-2H3,(H,28,29,30,31)
Chemical Name	1-[4-[5-[[3-(2-methylpyridin-3-yl)oxy-5-pyridin-2-ylsulfanylpyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]piperidin-1-yl]ethanone
Synonyms	AR453588; AR-453588
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
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

ln Vivo	In healthy C57BL/6J mice, AR453588 (3–30 mg/kg; oral) lowers postprandial blood glucose [1]. In ob/ob mice, AR453588 (3–30 mg/kg; oral; once daily for 14 days) showed anti-hyperglycemic activity over the course of the 14-day dose range [1]. Tmax, AUCinf, Vss, Cmax, and F of 1.0 mL/min/kg, 4.65 h μg/mL, 1.67 μg/mL, and 60.3%, respectively, were observed with AR453588 (10 mg/kg; po) treatment [1]. CL, AUCinf, Vss, and t1/2 of 21.6 mL/min/kg, 0.77 h μg/mL, 0.746 L/kg, and 1.28 h, respectively, were observed with AR453588 (1 mg/kg; iv) treatment [1].
Animal Protocol	Animal/Disease Models: Male diabetic ob/ob mice [1] Doses: 3, 10, 30 mg/kg Route of Administration: Orally, one time/day for 14 days Experimental Results: diminished fasting blood glucose and AUC OGTT in control animals on day 14 (Oral Glucose Tolerance Test). Animal/Disease Models: Male CD-1 mice [1] Doses: 10 mg/kg Route of Administration: po (pharmacokinetic/PK/PK analysis) Experimental Results: Tmax, AUCinf, Vss, Cmax and F were 1.0 mL/min/kg, respectively. 4.65 h μg/mL, 1.67 μg/mL and 60.3% respectively.
References	[1]. Discovery and preclinical development of AR453588 as an anti-diabetic glucokinase activator. Bioorg Med Chem. 2020 Jan 1;28(1):115232.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~192.44 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.81 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 25.0 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: ≥ 2.5 mg/mL (4.81 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 25.0 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: ≥ 2.5 mg/mL (4.81 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 25.0 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	1.9244 mL	9.6220 mL	19.2441 mL
	5 mM	0.3849 mL	1.9244 mL	3.8488 mL
	10 mM	0.1924 mL	0.9622 mL	1.9244 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.