1380672-07-0 Usage
Uses
Used in Pharmaceutical Industry:
G007-LK is used as a tankyrase inhibitor for its potent and selective inhibition of tankyrase enzymes (TNKS1/PARP5a/ARTD5 and TNKS2/PARP5b/ARTD6) in auto-PARsylation assays. This makes it a promising candidate for the development of therapeutic agents targeting tankyrase enzymes.
Used in Cancer Research:
G007-LK is used as an inhibitor of Wnt3a-induced reporter activity in human and murine cell cultures, making it a valuable tool for studying the role of tankyrase enzymes in cancer cell growth and proliferation.
Used in Colorectal Cancer Treatment:
G007-LK is used as an inhibitor of colony formation in vitro and tumor expansion in mice in vivo for two CRC lines, COLO-320DM & SW403. Its application in this context highlights its potential as a therapeutic agent for colorectal cancer treatment.
Biological Activity
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].
Biochem/physiol Actions
Cell permeable: yes
references
[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.
Check Digit Verification of cas no
The CAS Registry Mumber 1380672-07-0 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,3,8,0,6,7 and 2 respectively; the second part has 2 digits, 0 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 1380672-07:
(9*1)+(8*3)+(7*8)+(6*0)+(5*6)+(4*7)+(3*2)+(2*0)+(1*7)=160
160 % 10 = 0
So 1380672-07-0 is a valid CAS Registry Number.
1380672-07-0Relevant articles and documents
Structural basis and SAR for G007-LK, a lead stage 1,2,4-triazole based specific tankyrase 1/2 inhibitor
Voronkov, Andrew,Holsworth, Daniel D.,Waaler, Jo,Wilson, Steven R.,Ekblad, Bie,Perdreau-Dahl, Harmonie,Dinh, Huyen,Drewes, Gerard,Hopf, Carsten,Morth, Jens P.,Krauss, Stefan
, p. 3012 - 3023 (2013/06/04)
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 ? 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. Our study provides a significantly optimized compound for targeting TNKS1/2 in vitro and in vivo.
TRIAZOLE DERIVATIVES AS WNT SIGNALING PATHWAY INHIBITORS
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, (2012/06/30)
The present invention relates to compounds of formula (I), to processes for their preparation, to pharmaceutical formulations containing such compounds and to their use in therapy: Such compounds find particular use in the treatment and/or prevention of conditions or diseases which are affected by over-activation of signaling in the Wnt pathway and increased presence of nuclear β-catenin. For example, these may be used in preventing and/or retarding proliferation of tumor cells and metastasis, for example carcinomas such as colon carcinomas.
