Evogliptin (DA-1229) tartrat is an orally bioavailable DPP4 inhibitor (antagonist) with significant and durable hypoglycemic effects in mouse models. Evogliptin tartrat also inhibits the generation of inflammatory and fibrotic signals in hepatocytes by inducing autophagy. Evogliptin tartrat is indicated for treating type 2 diabetes, osteoporosis, renal impairment, and chronic liver inflammation.

Physicochemical Properties

Molecular Formula	C23H32F3N3O9
Molecular Weight	551.510097503662
Exact Mass	551.209
CAS #	1222102-51-3
Related CAS #	Evogliptin;1222102-29-5
PubChem CID	135395528
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	6
Hydrogen Bond Acceptor Count	13
Rotatable Bond Count	10
Heavy Atom Count	38
Complexity	692
Defined Atom Stereocenter Count	4
SMILES	FC1C=C(C(=CC=1C[C@H](CC(N1CCNC([C@H]1COC(C)(C)C)=O)=O)N)F)F.O[C@@H](C(=O)O)[C@H](C(=O)O)O
InChi Key	RBBXDAJRSNHIJZ-DLDKMZOSSA-N
InChi Code	InChI=1S/C19H26F3N3O3.C4H6O6/c1-19(2,3)28-10-16-18(27)24-4-5-25(16)17(26)8-12(23)6-11-7-14(21)15(22)9-13(11)20;5-1(3(7)8)2(6)4(9)10/h7,9,12,16H,4-6,8,10,23H2,1-3H3,(H,24,27);1-2,5-6H,(H,7,8)(H,9,10)/t12-,16-;1-,2-/m11/s1
Chemical Name	(3R)-4-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-[(2-methylpropan-2-yl)oxymethyl]piperazin-2-one;(2R,3R)-2,3-dihydroxybutanedioic acid
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

ln Vitro	In PWM-induced H9 Th1 cells, evogliptin tartrate (2.49 mM; 12 h) can efficiently decrease the activity of the mDPP4 (membrane DPP4) enzyme [1]. In primary hepatocytes of ATG7f/f-Cre+ mice, evogliptin tartrate induces autophagy, which inhibits inflammatory and fibrotic signaling [2].
ln Vivo	In HFD/STZ mice, evogliptin tartrate (100, 300 mg/kg; animal feed; once daily for 10 weeks) reduces insulin resistance and glucose intolerance [3].
Cell Assay	Cell Viability Assay[1] Cell Types: H9 Th1 cells (Pokeweed mitogen (PWM) induced) Tested Concentrations: 2.49 mM (1 µg/mL) Incubation Duration: 12 hrs (hours) Experimental Results: Effective inhibition of mDPP4 (membrane DPP4) at a certain dose ) activity-dependent manner, but did not affect the cytokine profile or cell viability in PWM-activated CD4+CD26+ H9 Th1 cells.
Animal Protocol	Animal/Disease Models: Male ICR mouse (4 weeks old; HFD/STZ mouse model) [3]. Doses: 100, 300 mg/kg Route of Administration: Animal feed; one time/day for 10 weeks Experimental Results: Blood glucose levels diminished starting from the second week and continued during the 300 mg/kg treatment period until 10 weeks. HbA1c levels were Dramatically diminished at a dose of 300 mg/kg. Dramatically diminished 6-hour fasting blood glucose levels in a dose-dependent manner.
References	[1]. Effects of the Antidiabetic Drugs Evogliptin and Sitagliptin on the Immune Function of CD26/DPP4 in Th1 Cells. Biomol Ther (Seoul). 2021 Mar 1;29(2):154-165. [2]. Evogliptin Directly Inhibits Inflammatory and Fibrotic Signaling in Isolated Liver Cells. International Journal of Molecular Sciences, 2022, 23(19): 11636. [3]. Hepatic role in an early glucose-lowering effect by a novel dipeptidyl peptidase 4 inhibitor, evogliptin, in a rodent model of type 2 diabetes. Eur J Pharmacol. 2016 Jan 15;771:65-76. [4]. Evogliptin: a new dipeptidyl peptidase inhibitor for the treatment of type 2 diabetes. Expert Opin Pharmacother. 2016 Jun;17(9):1285-93.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~181.32 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.53 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 (4.53 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 (4.53 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	1.8132 mL	9.0660 mL	18.1320 mL
	5 mM	0.3626 mL	1.8132 mL	3.6264 mL
	10 mM	0.1813 mL	0.9066 mL	1.8132 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.