BMS-820132 is an orally bioactive, partial glucokinase activator with an AC50 of 29 nM. BMS-820132 reduces glucose levels in the normal rat glucose tolerance test (OGTT) model but not in Zucker diabetic obese (ZDF) rats. BMS-820132 has pharmacological toxicity secondary to potent GK activation.

Physicochemical Properties

Molecular Formula	C26H33N6O7P
Molecular Weight	572.549986600876
Exact Mass	572.214
CAS #	1001419-18-6
PubChem CID	58265877
Appearance	White to off-white solid powder
LogP	1.8
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	13
Heavy Atom Count	40
Complexity	884
Defined Atom Stereocenter Count	0
SMILES	P(CN1C=CC(NC(C2C=C(C=C(C=2)OC2=CN=C(C=N2)C(N2CCC2)=O)OC(C)C)=O)=N1)(=O)(OCC)OCC
InChi Key	OYUDYQMFVRHPIY-UHFFFAOYSA-N
InChi Code	InChI=1S/C26H33N6O7P/c1-5-36-40(35,37-6-2)17-32-11-8-23(30-32)29-25(33)19-12-20(38-18(3)4)14-21(13-19)39-24-16-27-22(15-28-24)26(34)31-9-7-10-31/h8,11-16,18H,5-7,9-10,17H2,1-4H3,(H,29,30,33)
Chemical Name	3-[5-(azetidine-1-carbonyl)pyrazin-2-yl]oxy-N-[1-(diethoxyphosphorylmethyl)pyrazol-3-yl]-5-propan-2-yloxybenzamide
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 (e.g. under nitrogen), avoid exposure to moisture and light.
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	BMS-820132 (Compound 31) (3 μmol/kg, 30 μmol/kg; minimum; single dose) reduces contact levels of high-fat diet-induced body weight (DIO) electrodes in the baseline tolerance test (OGTT) [1] BMS -820132 (10-200 mg/kg; lateral; once daily for 1 month) resulted in normal weight recovery but had no effect on ZDF development, suggesting that BMS-820132 toxicity is secondary to the potent GK BMS-820132 ( 10 mg/kg-120 mg/kg; lateral; once daily for 1 month) had no significant effect on food consumption in dogs [2]. Pharmacokinetic analysis in animal models [1] Route Dose (mg/kg) Cmax (μM) Tmax (h) AUC0-24 h (μM·h) T1/2 (h) CLTp (mL/min/kg ) Vss (L /kg) F (L/kg) Mouse iv 2.5 24.9 2.1 2.9 0.3 po 5 14.1 0.5 49.7 100 Rat iv 2.5 16.6 0.9 4.4 0.3 po 5 13.0 0.9 29.5 90 Dog iv 3 12.3 1.8 7.2 0 .5 po 3 4.9 0.8 8.0 66 Monkey IV 3 3.8 1.9 22.7 1.1 po 3 3.8 1.3 0.57 15
Animal Protocol	Animal/Disease Models: Zucker diabetic obese (ZDF) rat and normal SD rat [2] Doses: 10 mg/kg, 50 mg/kg, 200 mg /kg Route of Administration: PO; one time/day for 1 month Experimental Results: Starting from day 7, body weight gain was diminished in SD rats (11% lower than controls), but not in ZDF rats. Animal/Disease Models: Beagle [2] Doses: 10 mg/kg, 60 mg/kg, 120 mg/kg Route of Administration: PO; one time/day for 1 month Experimental Results: There was no significant difference in food consumption in the dog model .
References	[1]. Discovery of a Partial Glucokinase Activator Clinical Candidate: Diethyl ((3-(3-((5-(Azetidine-1-carbonyl)pyrazin-2-yl)oxy)-5-isopropoxybenzamido)-1H-pyrazol-1-yl)methyl)phosphonate (BMS-820132). J Med Chem. 2022;65(5):4291-4317.

Solubility Data

Solubility (In Vitro)

DMSO : ~25 mg/mL (~43.66 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.37 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 2: ≥ 2.5 mg/mL (4.37 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	1.7466 mL	8.7329 mL	17.4657 mL
	5 mM	0.3493 mL	1.7466 mL	3.4931 mL
	10 mM	0.1747 mL	0.8733 mL	1.7466 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.