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863405-60-1

863405-60-1 Structure

863405-60-1 Structure
IdentificationBack Directory
[Name]

JW74
[CAS]

863405-60-1
[Synonyms]

JW74
JW74;JW 74
JW74 >=98% (HPLC)
4-[4-(4-Methoxyphenyl)-5-[[[3-(4-methylphenyl)-1,2,4-oxadiazol-5-yl]methyl]thio]-4H-1,2,4-triazol-3-yl]-pyridine
Pyridine, 4-[4-(4-methoxyphenyl)-5-[[[3-(4-methylphenyl)-1,2,4-oxadiazol-5-yl]methyl]thio]-4H-1,2,4-triazol-3-yl]-
[Molecular Formula]

C24H20N6O2S
[MDL Number]

MFCD07048962
[MOL File]

863405-60-1.mol
[Molecular Weight]

456.52
Chemical PropertiesBack Directory
[Boiling point ]

699.4±65.0 °C(Predicted)
[density ]

1.35±0.1 g/cm3(Predicted)
[storage temp. ]

2-8°C
[solubility ]

DMSO: ≥20mg/mL
[form ]

powder
[pka]

1.63±0.10(Predicted)
[color ]

white to beige
Safety DataBack Directory
[WGK Germany ]

3
Hazard InformationBack Directory
[Description]

Tankyrases (TNKS) are poly(ADP-ribose) polymerases (PARPs) that cleave NAD+ to produce nicotinamide and ADP-ribose, which is then covalently attached to an acceptor protein in a process known as poly(ADP-ribosyl)ation. TNKS have key roles in the Wnt signaling pathway as part of the β-catenin destruction complex. JW 74 is an inhibitor of the catalytic PARP domain of TNKS1/2 that blocks canonical Wnt signaling with an IC50 value of 790 nM. It increases the levels of Axin2 and decreases β-catenin levels in colorectal cancer (CRC) cells, leading to down-regulation of Wnt target genes. JW 74 inhibits the growth of CRC xenograft tumors in mice. JW 74 induces apoptosis and differentiation in osteosarcoma cell lines.
[Uses]

JW 74 is an inhibitor that affects cell cycle progression and induces apoptosis and differentiation in osteosarcoma cell lines.
[in vitro]

previous study found that jw74 at the molecular level induced stabilization of axin2, a key component of the β-catenin destruction complex, leading to reduced levels of nuclear β-catenin. in addition, jw74 could induce reduced cell growth in all tested cell lines, partially due to a delay in cell cycle progression and partially because of an induction of caspase-3-mediated apoptosis. moreover, jw74 was able to induce the differentiation in u2os cells and also enhance differentiation of os cell lines that did not harbor a differentiation block [1].
[in vivo]

previous animal study found that the dose of 150 mg/kg of jw74 in apcmin model could reduce the small intestinal adenoma by 48% and was comparable with celecoxib or rofecoxib. furthermore, it was noteworthy that jw74 became rapidly cleared from the blood stream due to its poor in vivo stability [2].
[IC 50]

790 nm for canonical wnt signaling
[storage]

Store at +4°C
[References]

1. e. w. stratford, j. daffinrud, e. munthe, et al. the tankyrase-specific inhibitor jw74 affects cell cycle progression and induces apoptosis and differentiation in osteosarcoma cell lines. cancer med. 3(1), 36-46 (2014).2. waaler j et al. novel synthetic antagonists of canonical wnt signaling inhibit colorectal cancer cell growth. cancer res. 2011 jan 1;71(1):197-205.
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