G007-LK

Alias: G00 7LK; G007-LK; G007LK
Cat No.:V0307 Purity: ≥98%
G007-LK is a novel, potent and specific tankyrase (TNKS) 1/2 inhibitor with potential anticancer activity.
G007-LK Chemical Structure CAS No.: 1380672-07-0
Product category: PARP
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

G007-LK is a novel, potent and specific tankyrase (TNKS) 1/2 inhibitor with potential anticancer activity. Its respective IC50s for inhibiting TNKS 1/2 are 46 nM and 25 nM. ADP ribosylation of TNKS1 and TNKS2 was decreased by G007-LK. In vivo antitumor efficacy is also high, and it exhibits strong antiproliferative activity against a variety of cancer cells. G007-LK has an IC50 value of 0.05 μM and inhibits ST-Luc in HEK 293 cells that have been induced with Wnt3a. Using the GFP-TNKS1-transfected SW480 colorectal cancer cell line, G007-LK generates phosphorylated beta-catenin, beta-TrCP, and ubiquitin-containing highly dynamic and mobile degradasomes. G007-LK lowers nuclear and cytosolic β-catenin protein levels in the APC-mutant cell lines.

Biological Activity I Assay Protocols (From Reference)
Targets
TNKS2 ( IC50 = 25 nM ); TNKS1 ( IC50 = 46 nM )
ln Vitro

G007-LK exhibits strong inhibitory effects on both TNKS1 and TNKS2, as evidenced by its IC50 values of 46 nM and 25 nM, respectively, and its cellular IC50 of 50 nM. G007-LK has a high IC50 value (>25 μM) for CYP3A4 inhibition and exhibits no inhibition of PARP1 at doses up to 20 μM[1]. Hepatocellular carcinoma (HCC) cell growth is dose-dependently inhibited by G007-LK (0-20 μM). Additionally, in HCC cell lines, G007-LK decreases YAP levels by upregulating AMOTL1 and AMOTL2. Furthermore, G007-LK (0-20 μM) suppresses the proliferation of HCC cells by working in concert with MEK and AKT inhibitors[3].

ln Vivo
G007-LK exhibits an excellent pharmacokinetic profile in ICR mice.[1] In mice with LGR5+ intestinal stem cells, G007-LK (100 mg/kg chow, p.o.) dramatically decreases lineage tracing. To specifically target LGR5+ WNT-dependent intestinal stem cells in Lgr5-EGFP-CreERT2;R26R-tdTomato mice, G007-LK (100 mg/kg chow, p.o.) is administered. The suppressor of canonical WNT signaling is G007-LK (10, 50 mg/kg, p.o.). Moreover, there is no discernible change in the duodenal morphology when G007-LK (100, 1000 mg/kg chow, p.o.) is administered.
Enzyme Assay
TNKS1 and TNKS2 in vitro biochemical assays: G007-LK inhibitory activity is examined twice against TNKS1, TNSK2 Chemiluminescent Assay Kits at different dosages (duplicates), and the luminescence is gauged using a GloMax Luminometer.
Cell Assay
In order to conduct assays on cell proliferation or apoptosis, SNU-449 and HLE cells are cultured in RPMI Medium supplemented with 10% fetal bovine serum (FBS), penicillin/streptomycin, and 5% CO2 at 37°C. Treatment options for HCC cells include 0.1% DMSO, 2.5 μM, 5 μM, 10 μM, 20 μM XAV-939 or G007-LK, either by itself or in combination with the AKT inhibitor MK-2206 (5 μM) or the MEK inhibitor U0126 (25 μM). The Cell Death Detection Elisa Plus Kit is used to measure apoptosis, and the BrdU Cell Proliferation Assay Kit is used to analyze cell proliferation[3].
Animal Protocol
Unless specifically noted, Lgr5-EGFP-Ires-CreERT2;R26R-Confetti mice, either single or double transgenic, are used in drug treatment experiments. G007-LK is given orally in two ways: either as a gavage (10 or 50 mg/kg body mass once daily; vehicle: 15% dimethylsulfoxide [DMSO], 17.5% Cremophor EL, 8.75% Miglyol 810 N, 8.75% ethanol in phosphate buffered saline [PBS]) or as an enriched chow (100 or 1000 mg G007-LK/kg chow ad libitum). This corresponds to a daily G007-LK dose of roughly 20 or 200 mg/kg body mass, respectively, for a mouse with a body mass of 25 g and consumption of approximately 5 g enriched diet/day. G007-LK treatments are administered for 9 or 21 days, starting at 5 weeks and 5 days for oral gavage treatment and 6 weeks for the administration of enriched chow, respectively[2].
References

[1]. Structural basis and SAR for G007-LK, a lead stage 1,2,4-triazole based specific tankyrase 1/2 inhibitor. J Med Chem. 2013 Apr 11;56(7):3012-23.

[2]. The tankyrase inhibitor G007-LK inhibits small intestine LGR5+ stem cell proliferation without altering tissue morphology. Biol Res. 2018 Jan 9;51(1):3.

[3]. Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade. PLoS One. 2017 Sep 6;12(9):e0184068.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C25H16CLN7O3S
Molecular Weight
529.96
Exact Mass
529.07
Elemental Analysis
C, 56.66; H, 3.04; Cl, 6.69; N, 18.50; O, 9.06; S, 6.05
CAS #
1380672-07-0
Appearance
Solid powder
SMILES
CS(=O)(=O)C1=CN=C(C=C1)C2=NN=C(N2C3=CC=CC=C3Cl)/C=C/C4=NN=C(O4)C5=CC=C(C=C5)C#N
InChi Key
HIWVLHPKZNBSBE-OUKQBFOZSA-N
InChi Code
InChI=1S/C25H16ClN7O3S/c1-37(34,35)18-10-11-20(28-15-18)24-31-29-22(33(24)21-5-3-2-4-19(21)26)12-13-23-30-32-25(36-23)17-8-6-16(14-27)7-9-17/h2-13,15H,1H3/b13-12+
Chemical Name
4-[5-[(E)-2-[4-(2-chlorophenyl)-5-(5-methylsulfonylpyridin-2-yl)-1,2,4-triazol-3-yl]ethenyl]-1,3,4-oxadiazol-2-yl]benzonitrile
Synonyms
G00 7LK; G007-LK; G007LK
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: 69~100 mg/mL (130.2~188.7 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.8869 mL 9.4347 mL 18.8693 mL
5 mM 0.3774 mL 1.8869 mL 3.7739 mL
10 mM 0.1887 mL 0.9435 mL 1.8869 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

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Biological Data
  • The XAV-939 and G007-LK Tankyrase inhibitors suppress HCC cell growth. PLoS One . 2017 Sep 6;12(9):e0184068.
  • Body mass, administration schemes and pharmacokinetics of G007-LK. Biol Res . 2018 Jan 9;51(1):3.
  • G007-LK specifically targets LGR5+ WNT-dependent intestinal stem cells. Biol Res . 2018 Jan 9;51(1):3.
  • G007-LK treatment reduced canonical WNT signalling. Biol Res . 2018 Jan 9;51(1):3.
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