JW74 - CAS 863405-60-1
Catalog number:
863405-60-1
Category:
Inhibitor
Not Intended for Therapeutic Use. For research use only.
COA:
Inquire
Targets:
PPAR
Description:
JW74 is a tankyrase-specific inhibitor. JW74 affects cell cycle progression and induces apoptosis and differentiation in osteosarcoma cell lines. At the molecular level, JW74 induces stabilization of AXIN2, a key component of the β-catenin destruction complex, resulting in reduced levels of nuclear β-catenin. At the functional level, JW74 induces reduced cell growth in all three tested cell lines, in part due to a delay in cell cycle progression and in part due to an induction of caspase-3-mediated apoptosis. Furthermore, JW74 induces differentiation in U2OS cells, which under standard conditions are resistant to osteogenic differentiation. JW74 also enhances differentiation of OS cell lines, which do not harbor a differentiation block.
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Purity:
0.98
Appearance:
white solid powder
Synonyms:
JW74; JW-74; JW 74
MSDS:
Inquire
Current Developer:
Oslo University
1.Atorvastatin protects vascular smooth muscle cells from TGF-β1-stimulated calcification by inducing autophagy via suppression of the β-catenin pathway.
Liu D1, Cui W, Liu B, Hu H, Liu J, Xie R, Yang X, Gu G, Zhang J, Zheng H. Cell Physiol Biochem. 2014;33(1):129-41. doi: 10.1159/000356656. Epub 2014 Jan 20.
BACKGROUND: Arterial calcification is a major event in the progression of atherosclerosis. It is reported that statins exhibit various protective effects against vascular smooth muscle cell (VSMC) inflammation and proliferation in cardiovascular remodeling. Although statins counteract atherosclerosis, the molecular mechanisms of statins on the calcium release from VSMCs have not been clearly elucidated.
2.The tankyrase-specific inhibitor JW74 affects cell cycle progression and induces apoptosis and differentiation in osteosarcoma cell lines.
Stratford EW1, Daffinrud J, Munthe E, Castro R, Waaler J, Krauss S, Myklebost O. Cancer Med. 2014 Feb;3(1):36-46. doi: 10.1002/cam4.170. Epub 2013 Dec 17.
Wnt/β-catenin is a major regulator of stem cell self-renewal and differentiation and this signaling pathway is aberrantly activated in a several cancers, including osteosarcoma (OS). Attenuation of Wnt/β-catenin activity by tankyrase inhibitors is an appealing strategy in treatment of OS. The efficacy of the tankyrase inhibitor JW74 was evaluated in three OS cell lines (KPD, U2OS, and SaOS-2) both at the molecular and functional level. At the molecular level, JW74 induces stabilization of AXIN2, a key component of the β-catenin destruction complex, resulting in reduced levels of nuclear β-catenin. At the functional level, JW74 induces reduced cell growth in all three tested cell lines, in part due to a delay in cell cycle progression and in part due to an induction of caspase-3-mediated apoptosis. Furthermore, JW74 induces differentiation in U2OS cells, which under standard conditions are resistant to osteogenic differentiation. JW74 also enhances differentiation of OS cell lines, which do not harbor a differentiation block.
3.Dl-3n-butyphthalide suppresses PDGF-BB-stimulated vascular smooth muscle cells proliferation via induction of autophagy.
Hu H1, Liu B1, Zuo Y1, Liu D1, Xie R1, Cui W2. Life Sci. 2016 Mar 8. pii: S0024-3205(16)30160-6. doi: 10.1016/j.lfs.2016.03.010. [Epub ahead of print]
AIMS: Vascular smooth muscle cells (VSMCs) played an important role in vascular remodeling. Dl-3-n-butylphthalide (NBP) was extracted as a pure component from seeds of Apium graveolens Linn (Chinese celery) for protecting neurons activity, but the role of NBP on VSMCs was not clearly clarified.
4.Structural basis and SAR for G007-LK, a lead stage 1,2,4-triazole based specific tankyrase 1/2 inhibitor.
Voronkov A1, Holsworth DD, Waaler J, Wilson SR, Ekblad B, Perdreau-Dahl H, Dinh H, Drewes G, Hopf C, Morth JP, Krauss S. J Med Chem. 2013 Apr 11;56(7):3012-23. doi: 10.1021/jm4000566. Epub 2013 Mar 29.
Tankyrases 1 and 2 (TNKS1/2) are promising pharmacological biotargets with possible applications for the development of novel anticancer therapeutics. A focused structure-activity relationship study was conducted based on the tankyrase inhibitor JW74 (1). Chemical analoging of 1 improved the 1,2,4-triazole based core and led to 4-{5-[(E)-2-{4-(2-chlorophenyl)-5-[5-(methylsulfonyl)pyridin-2-yl]-4H-1,2,4-triazol-3-yl}ethenyl]-1,3,4-oxadiazol-2-yl}benzonitrile (G007-LK), a potent, "rule of 5" compliant and a metabolically stable TNKS1/2 inhibitor. G007-LK (66) displayed high selectivity toward tankyrases 1 and 2 with biochemical IC50 values of 46 nM and 25 nM, respectively, and a cellular IC50 value of 50 nM combined with an excellent pharmacokinetic profile in mice. The PARP domain of TNKS2 was cocrystallized with 66, and the X-ray structure was determined at 2.8 Å resolution in the space group P3221. The structure revealed that 66 binds to unique structural features in the extended adenosine binding pocket which forms the structural basis for the compound's high target selectivity and specificity.
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CAS 863405-60-1 JW74

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