| Identification | Back Directory | [Name]
G007-LK | [CAS]
1380672-07-0 | [Synonyms]
G007-LK
CS-1659
G007 LK;G007LK
G007-LK;G007 LK;G007LK
Tankyrase 1/2 Inhibitor VI, G007-LK - Calbiochem
(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
4-[5-[(1E)-2-[4-(2-Chlorophenyl)-5-[5-(methylsulfonyl)-2-pyridinyl]-4H-1,2,4-triazol-3-yl]ethenyl]-1,3,4-oxadiazol-2-yl]benzonitrile
Benzonitrile, 4-[5-[(1E)-2-[4-(2-chlorophenyl)-5-[5-(methylsulfonyl)-2-pyridinyl]-4H-1,2,4-triazol-3-yl]ethenyl]-1,3,4-oxadiazol-2-yl]- | [Molecular Formula]
C25H16ClN7O3S | [MDL Number]
MFCD28167833 | [MOL File]
1380672-07-0.mol | [Molecular Weight]
529.96 |
| Chemical Properties | Back Directory | [Boiling point ]
817.3±75.0 °C(Predicted) | [density ]
1.47±0.1 g/cm3(Predicted) | [storage temp. ]
+2C to +8C | [solubility ]
≥26.5 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH | [form ]
White powder | [pka]
-1.68±0.10(Predicted) | [color ]
Off-white to yellow |
| Hazard Information | Back Directory | [Uses]
G007-LK is a potent and selective inhibitor of TNKS1 and TNKS2, with IC50s of 46 nM and 25 nM, respectively. | [General Description]
A cell-permeable, triazolyl-vinyl-oxadiazole compound that targets adenosine site of the NAD+ pocket in the TNKS PARP domain and acts as a potent and highly selective tankyrase inhibitor (IC50 = 33 and 26 nM, respectively, against TNKS1/PARP5a/ARTD5 and TNKS2/PARP5b/ARTD6 in auto-PARsylation assays), effectively inhibiting murine Wnt3a-induced reporter activity in human HEK293 and murine 10T1/2 cultures (ICmax ~300 and 600 nM, respectively). Shown to display little or no inhibitory potency (IC50 >10 μM) toward 7 other PARP enzymes (PARP1, 2, 3, 6, 7,10,11), 90 kinases, 16 phosphatases, and 75 GPCRs (IC50 >10 μM). Shown to inhibit two CRC lines, COLO-320DM & SW403, colony formation in vitro (200 nM) and tumor expansion in mice in vivo (20 mg/kg via daily i.p.), although G007-LK toxicity is observed at higher dosages (≥30 mg/kg/12 h or 60 mg/kg/d via i.p.).
Please note that the molecular weight for this compound is batch-specific due to variable water content. | [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 | [in vivo]
G007-LK displays great pharmacokinetic profile in ICR mice[1]. G007-LK (100 mg/kg chow, p.o.) significantly reduces lineage tracing from LGR5+ intestinal stem cells in mice. G007-LK (100 mg/kg chow, p.o.) specifically targets LGR5+ WNT-dependent intestinal stem cells in Lgr5-EGFP-CreERT2;R26R-tdTomato mice. G007-LK (10, 50 mg/kg, p.o.) also suppressses canonical WNT signalling. Furthermore, G007-LK (100, 1000 mg/kg chow, p.o) shows no effect on the alteration of duodenal morphology[2]. | [IC 50]
TNKS2: 25 nM (IC50); TNKS1: 46 nM (IC50) | [storage]
Store at -20°C | [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. |
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