Name: G007-LK
Price: 292.00 USD

- Overview
  - Please contact us at for specific academic pricing.
    
    Background
    
    G007-LK is a potent and specific inhibitor of tankyrase 1/2 with IC50 values of 46 and 25 nM [1].
    The telomeric repeat factor 1 (TRF1)-interacting ankyrin-related ADP-ribose polymerase 1 (tankyrase 1,TNKS1) and tankyrase 2 (TNKS2) belong to the subgroup of poly(ADP-ribosyl)ating polymerases and regulate the assembly and disassembly of large polymerized structures [1].
    G007-LK is a potent and specific tankyrase 1/2 inhibitor. G007-LK reduced auto-poly-(ADP ribosy)lation of TNKS1 and TNKS2 with IC50 values of 46 nM and 25 nM, respectively. In Wnt3a-induced HEK 293 cells, G007-LK inhibited ST-Luc with IC50 value of 0.05 μM [1]. In SW480 colorectal cancer cell line transfected with GFP-TNKS1, G007-LK induces highly dynamic and mobile degradasomes containing phosphorylated beta-catenin, beta-TrCP and ubiquitin [2]. In the APC-mutant cell lines, G007-LK reduces cytosolic and nuclear β-catenin protein levels [3].
    In mice bearing COLO-320DM cell xenografts, G007-LK (20 mg/kg twice daily or 40 mg/kg daily) concentration-dependently inhibited tumor growth by 61% and 48%, respectively. Also, G007-LK reduced the levels of TNKS1/2 and β-catenin, and stabilized AXIN1/2 [3].
    
    [1]. Voronkov A, Holsworth DD, Waaler J, et al. Structural basis and SAR for G007-LK, a lead stage 1,2,4-triazole based specific tankyrase 1/2 inhibitor. J Med Chem, 2013, 56(7): 3012-3023.
    [2]. Thorvaldsen TE, Pedersen NM, Wenzel EM, et al. Structure, Dynamics and Functionality of Tankyrase Inhibitor-induced Degradasomes. Mol Cancer Res, 2015, pii: molcanres.0125.2015.
    [3]. Lau T, Chan E, Callow M, et al. A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth. Cancer Res, 2013, 73(10): 3132-3144.
- Properties
  - Alternative Name
    
    (E)-4-(5-(2-(4-(2-chlorophenyl)-5-(5-(methylsulfonyl)pyridin-2-yl)-4H-1,2,4-triazol-3-yl)vinyl)-1,3,4-oxadiazol-2-yl)benzonitrile
    
    CAS Number
    
    1380672-07-0
    
    Molecular Formula
    
    C25H16ClN7O3S
    
    Molecular Weight
    
    529.96
    
    Appearance
    
    A solid
    
    Purity
    
    98.10%
    
    Solubility
    
    ≥26.5 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH
    
    Storage
    
    Store at -20°C
    
    * For Research Use Only
- Reference
  - 1. Leibold J, Ruscetti M, et al. "Somatic Tissue Engineering in Mouse Models Reveals an Actionable Role for WNT Pathway Alterations in Prostate Cancer Metastasis." Cancer Discov. 2020;10(7):1038-1057.nbsp;PMID:32376773
    2. Kim S, Han S, et al. "Tankyrase inhibition preserves osteoarthritic cartilage by coordinating cartilage matrix anabolism via effects on SOX9 PARylation." Nat Commun. 2019 Oct 25;10(1):4898.nbsp;PMID:31653858
    3. Li N, Wang Y, et al. "Tankyrase disrupts metabolic homeostasis and promotes tumorigenesis by inhibiting LKB1-AMPK signalling." Nat Commun. 2019 Sep 25;10(1):4363.nbsp;PMID:31554794
    4. Jia J, Qiao Y, et al. "Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade." PLoS One. 2017 Sep 6;12(9):e0184068. PMID:28877210

G007-LK

G007-LK

Background

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