TMPA is a high-affinity Nur77 antagonist, and binding to Nur77 results in the release and shuttling of LKB1 in the cytoplasm to activate AMPKα. TMPA can effectively lower blood glucose and alleviate insulin resistance in type II db/db, high-fat diet and streptozotocin-induced diabetic mice. TMPA can reduce RICD of human T cells and can also be utilized in the research on cancer and T cell apoptosis disorders.

Physicochemical Properties

Molecular Formula	C21H32O6
Molecular Weight	380.4752
Exact Mass	380.219
CAS #	1258275-73-8
Related CAS #	1258275-73-8
PubChem CID	60146245
Appearance	Light yellow to yellow solid
Density	1.1±0.1 g/cm3
Boiling Point	480.0±45.0 °C at 760 mmHg
Flash Point	205.8±28.8 °C
Vapour Pressure	0.0±1.2 mmHg at 25°C
Index of Refraction	1.491
LogP	5.25
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	14
Heavy Atom Count	27
Complexity	438
Defined Atom Stereocenter Count	0
SMILES	O=C(C1=C([H])C(=C(C(=C1C([H])([H])C(=O)OC([H])([H])C([H])([H])[H])OC([H])([H])[H])OC([H])([H])[H])OC([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H]
InChi Key	WCYMJQXRLIDSAQ-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H32O6/c1-6-8-9-10-11-12-17(22)15-13-18(24-3)21(26-5)20(25-4)16(15)14-19(23)27-7-2/h13H,6-12,14H2,1-5H3
Chemical Name	ethyl 2-(2,3,4-trimethoxy-6-octanoylphenyl)acetate
Synonyms	TMPA
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 Vitro	TMPA (5, 10, 20, 40, 80 μM; 6 hours or 10 μM; 0.5, 1, 3, 6, 12, 24, 36, 48 hours) antagonizes Nur77-LKB1 ligated TMPA ( 10 μM; 6 hours) improves the LKB1-AMPKα response but lowers the LKB1-Nur77 response in Lo2 cells under physiological conditions [1]. TMPA directly interacts with LBD with a specific structural picture [1]. TMPA (10, 20 μM; 6 h) promotes LKB1 nuclear export and activates AMPKα in Lo2 cells [1]. TMPA (10, 50, 100 μM; 4 h) damages human T cells RICD (restimulation-induced [1].
ln Vivo	In individuals with type II diabetes, TMPA (50 mg/kg; intraperitoneal injection; single dose daily for 19 days) can lower blood pressure and enhance diabetic tolerance [1].
Cell Assay	Cell viability assay [2] Cell Types: T cell Tested Concentrations: 10, 50, 100 μM Incubation Duration: 4 h Experimental Results: Dramatically diminished T cell RICD (cell death) in a dose-dependent manner [2]. Western Blot Analysis[1] Cell Types: Liver LO2 Cells Tested Concentrations: 10, 20 µM Incubation Duration: 6 hrs (hours) Experimental Results: Experimental Results: Increased LKB1 Ser428 phosphorylation. Western Blot Analysis[1] Cell Types: Liver LO2 cells Tested Concentrations: 5, 10, 20, 40, 80 µM Incubation Duration: 6 hrs (hours) Experimental Results: AmPKα phosphorylation increased in a dose- and time-dependent manner. At a concentration of 10 µM, the LKB1-AmPKα interaction is rescued by reducing the nur77-lKb1 interaction.
Animal Protocol	Animal/Disease Models: Male C57BL/KsJ-Leprdb/Leprdb (db/db ) mice (10 weeks old; type II diabetes model) [1]. Doses: 50 mg/kg Route of Administration: intraperitoneal (ip) injection; daily for 19 days. Experimental Results: Blood glucose diminished Dramatically on day 7 and persisted for the remainder of the test. Increases the amount of phosphorylated AMPKα in mouse liver.
References	[1]. The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK. Nat Chem Biol. 2012 Nov;8(11):897-904. [2]. Modulation of T-cell apoptosis by small molecule compounds targeting the nuclear orphan receptor Nur 77. (2018).
Additional Infomation	Ethyl (2,3,4-trimethoxy-6-octanoylphenyl)acetate is an aromatic ketone.

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 100 mg/mL (262.8 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.57 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 (6.57 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	2.6283 mL	13.1413 mL	26.2826 mL
	5 mM	0.5257 mL	2.6283 mL	5.2565 mL
	10 mM	0.2628 mL	1.3141 mL	2.6283 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.