JW74 antagonizes LiCl-induced activation of canonical Wnt signaling with IC50 of 420 nM.

Physicochemical Properties

Molecular Formula	C24H20N6O2S
Molecular Weight	456.5196
Exact Mass	456.136
CAS #	863405-60-1
PubChem CID	16013152
Appearance	White to off-white solid powder
Density	1.4±0.1 g/cm3
Boiling Point	699.4±65.0 °C at 760 mmHg
Flash Point	376.8±34.3 °C
Vapour Pressure	0.0±2.2 mmHg at 25°C
Index of Refraction	1.700
LogP	6.37
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	7
Heavy Atom Count	33
Complexity	596
Defined Atom Stereocenter Count	0
InChi Key	KRIKILRRJCIWNB-UHFFFAOYSA-N
InChi Code	InChI=1S/C24H20N6O2S/c1-16-3-5-17(6-4-16)22-26-21(32-29-22)15-33-24-28-27-23(18-11-13-25-14-12-18)30(24)19-7-9-20(31-2)10-8-19/h3-14H,15H2,1-2H3
Chemical Name	5-[[4-(4-methoxyphenyl)-5-pyridin-4-yl-1,2,4-triazol-3-yl]sulfanylmethyl]-3-(4-methylphenyl)-1,2,4-oxadiazole
Synonyms	JW 74; JW-74; JW74
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 ST-Luc experiment, JW74 exhibits decreased canonical Wnt signaling, with an IC50 of 790 nM [1]. The MTS assay was used to examine how tankyrase inhibition affected the viability of the cells. Compared to cells treated with DMSO, the viability of U2OS cells treated with 10 μM JW74 for 72 hours was reduced to 80%. After treating U2OS with DMSO or 10 uM JW74 for 48 hours, the expression marker Ki-67 was also measured using flow cytometry. In cells treated with DMSO, Ki-67 expression was 97.5%; in cells treated with JW74, it was 86.7% [2].
ln Vivo	The in vivo effectiveness of JW74 was investigated using SW480 cell xenografts. Relatively higher doses of JW74 (150 or 300 mg/kg) were utilized because the chemical demonstrates strong biological activity as indicated by human liver microsomal study (t1/2=2.5 min) and pharmacokinetic analysis (after each oral injection). Rapidly degraded in the body. ( t1/2=30 minutes, intravenous injection: t1/2=15 minutes). Identification of the presence of JW74 in tumors and plasma by mass spectrometry. JW74 concentrations in tumors ranged from 4.2 to 72.1 μmol/kg for JW74 150 mg/kg, 1.9 to 11.1 μmol/kg for JW74 300 mg/kg, and JW74 concentrations in plasma were 2.8 μM at both dosages [1].
References	[1]. Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth. Cancer Res. 2011 Jan 1;71(1):197-205. [2]. The tankyrase-specific inhibitor JW74 affects cell cycle progression and induces apoptosis and differentiation in osteosarcoma cell lines. Cancer Med. 2014 Feb;3(1):36-46.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 50 mg/mL (~109.52 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.75 mg/mL (6.02 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 27.5 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: ≥ 2.75 mg/mL (6.02 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 27.5 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	2.1905 mL	10.9524 mL	21.9048 mL
	5 mM	0.4381 mL	2.1905 mL	4.3810 mL
	10 mM	0.2190 mL	1.0952 mL	2.1905 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.