Velagliflozin proline hydrate is the clinical form of Velagliflozin. Velagliflozin is an orally bioavailable sodium-glucose cotransporter 2 (SGLT2) inhibitor (antagonist) with antidiabetic activity. Specifically, Velagliflozin decreases renal glucose reabsorption and promotes glucosuria, thereby lowering blood glucose and insulin concentrations.

Physicochemical Properties

Molecular Formula	C28H36N2O8
Molecular Weight	528.59
Exact Mass	528.247
CAS #	1661838-94-3
Related CAS #	Velagliflozin;946525-65-1;Velagliflozin proline;1539295-26-5
PubChem CID	156337572
Appearance	White to light yellow solid-liquid Mixture
Hydrogen Bond Donor Count	7
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	6
Heavy Atom Count	38
Complexity	696
Defined Atom Stereocenter Count	6
SMILES	C1C[C@H](NC1)C(=O)O.C1CC1C2=CC=C(C=C2)CC3=C(C=CC(=C3)[C@H]4[C@@H]([C@H]([C@@H]([C@H](O4)CO)O)O)O)C#N.O
InChi Key	SSNUQDYITAZVPB-YAKUHWJSSA-N
InChi Code	InChI=1S/C23H25NO5.C5H9NO2.H2O/c24-11-17-8-7-16(23-22(28)21(27)20(26)19(12-25)29-23)10-18(17)9-13-1-3-14(4-2-13)15-5-6-15;7-5(8)4-2-1-3-6-4;/h1-4,7-8,10,15,19-23,25-28H,5-6,9,12H2;4,6H,1-3H2,(H,7,8);1H2/t19-,20-,21+,22-,23+;4-;/m10./s1
Chemical Name	2-[(4-cyclopropylphenyl)methyl]-4-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]benzonitrile;(2S)-pyrrolidine-2-carboxylic acid;hydrate
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

Targets	SGLT2
ln Vitro	An inhibitor of sodium-glucose cotransporter 2 (SGLT2) with antidiabetic properties is velagliflozin proline hydrate [1].
ln Vivo	In cats, velagliflozin proline hydrate (1 mg/kg, oral, single dose) lowers respiratory exchange ratio and raises albumin, cholesterol, beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), and urine glucose excretion [1]. Because it lessens the hyperinsulin response to dietary nonstructural carbohydrates (NSC), velagliflozin proline hydrate (0.3 mg/kg; PO; once daily for 18 days) is well tolerated and may be used to treat insulin dysregulation and prevent spondylosis in ponies. Laminitis [2].
References	[1]. Effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor velagliflozin, a new drug with therapeutic potential to treat diabetes in cats. J Vet Pharmacol Ther. 2018 Apr;41(2):266-273. [2]. The sodium-glucose co-transporter 2 inhibitor velagliflozin reduces hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies. PLoS One. 2018 Sep 13;13(9):e0203655.

Solubility Data

Solubility (In Vitro)

DMSO: 200 mg/mL (378.37 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5 mg/mL (9.46 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 50.0 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: ≥ 5 mg/mL (9.46 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 50.0 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: ≥ 5 mg/mL (9.46 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 50.0 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	1.8918 mL	9.4591 mL	18.9183 mL
	5 mM	0.3784 mL	1.8918 mL	3.7837 mL
	10 mM	0.1892 mL	0.9459 mL	1.8918 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.