TM-N1324 is an agonist of G protein-coupled receptor 39 (GPR39). In the presence of Zn2+, the EC50s for human and mouse GPR39 are 9 nM and 5 nM respectively. In the absence of Zn2+, the EC50s are 9 nM and 5 nM, respectively. The EC50s of human and mouse GPR39 are 280 nM and 180 nM respectively.

Physicochemical Properties

Molecular Formula	C18H13CLFN7O
Molecular Weight	397.793524503708
Exact Mass	397.085
CAS #	1144477-35-9
PubChem CID	135634901
Appearance	White to off-white solid powder
Density	1.8±0.1 g/cm3
Boiling Point	699.3±65.0 °C at 760 mmHg
Flash Point	376.7±34.3 °C
Vapour Pressure	0.0±2.3 mmHg at 25°C
Index of Refraction	1.834
LogP	1.96
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	2
Heavy Atom Count	28
Complexity	615
Defined Atom Stereocenter Count	0
InChi Key	CYQNVXRIWKKWQG-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H13ClFN7O/c1-8-14-11(10-3-2-9(20)4-12(10)19)5-13(28)25-17(14)27(26-8)18-15-16(22-6-21-15)23-7-24-18/h2-4,6-7,11H,5H2,1H3,(H,25,28)(H,21,22,23,24)
Chemical Name	4-(2-chloro-4-fluorophenyl)-3-methyl-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[3,4-b]pyridin-6-one
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

In the absence of Zn2+ and with potencies of 280 nM and 9 nM, respectively, TM-N1324 effectively activates human GPR39. TM-N1324 exhibited comparable potencies of 180 nM and 5 nM against mouse GPR39. It was also discovered that TM-N1324 has good in vitro ADME characteristics. At pH 7.0, TM-N1324 has remarkable water solubility, with a concentration of 65 μM. Somatostatin measurements verified that the GPR39 agonist TM-N1324 raised somatostatin secretion by 53 percent [1].

References

[1]. Model-Based Discovery of Synthetic Agonists for the Zn2+-Sensing G-Protein-Coupled Receptor 39 (GPR39) Reveals Novel Biological Functions. J Med Chem. 2017 Feb 9;60(3):886-898.

Solubility Data

Solubility (In Vitro)

DMSO : ~5 mg/mL (~12.57 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 1.22 mg/mL (3.07 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.2 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: ≥ 1.22 mg/mL (3.07 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 12.2 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5139 mL	12.5694 mL	25.1389 mL
	5 mM	0.5028 mL	2.5139 mL	5.0278 mL
	10 mM	0.2514 mL	1.2569 mL	2.5139 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.