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Chemical Structure| 1380672-07-0 Chemical Structure| 1380672-07-0

Structure of G007-LK
CAS No.: 1380672-07-0

Chemical Structure| 1380672-07-0

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G007-LK is a potent and selective tankyrase inhibitor with IC50 of 46 nM and 25 nM for TNKS1/2, respectively.

Synonyms: Tankyrase 1/2 Inhibitor VI

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Product Details of G007-LK

CAS No. :1380672-07-0
Formula : C25H16ClN7O3S
M.W : 529.96
SMILES Code : ClC1=C(N2C(/C=C/C3=NN=C(O3)C4=CC=C(C=C4)C#N)=NN=C2C5=CC=C(C=N5)S(C)(=O)=O)C=CC=C1
Synonyms :
Tankyrase 1/2 Inhibitor VI
MDL No. :MFCD28167833
InChI Key :HIWVLHPKZNBSBE-OUKQBFOZSA-N
Pubchem ID :67960134

Safety of G007-LK

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of G007-LK

epigenetics
DNA

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
H58 cells 0, 0.1, 0.5, 1, 2, 4 μM 96 h To evaluate the cytotoxicity of G007-LK on H58 cells, the results showed that H58 cells were not sensitive to G007-LK, as IC50 was not reached even at a concentration of 4 μM. PMC7316603
SH-SY5Y cells 1 μM 1 h G007-LK significantly reduced FUS granule formation PMC9330637
HEK293A cells 5 μM 12 h G007-LK induced AMPK activation without altering LKB1/AMPK levels. PMC6761205
U2OS cells 5 μM 12 h G007-LK induced AMPK activation. PMC6761205
COLO 320DM 1 µM 24 h Inhibition of WNT/β-catenin signaling, reduction of MYC and CCND1 expression, leading to impaired cell growth PMC8313754
UO-31 1 µM 24 h Inhibition of YAP signaling, reduction of MYC and CCND1 expression, leading to impaired cell growth PMC8313754
OVCAR-4 1 µM 24 h Inhibition of WNT/β-catenin and YAP signaling, reduction of MYC and CCND1 expression, leading to impaired cell growth PMC8313754
ABC-1 1 µM 24 h Inhibition of PI3K/AKT signaling, reduction of MYC and CCND1 expression, leading to impaired cell growth PMC8313754
shApc organoids 1μM 3 days To evaluate the effect of G007-LK on shApc organoids, results showed that G007-LK-treated shApc organoids underwent rapid cell cycle arrest, and induced Krt20 expression while reducing Lgr5 expression. PMC6774804
ApcMin organoids 1μM 3 days To evaluate the effect of G007-LK on ApcMin organoids, results showed that G007-LK-treated ApcMin organoids maintained a proliferative phenotype, with no significant changes in Krt20 and Lgr5 expression observed. PMC6774804

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Diabetic mouse model Intraperitoneal injection 30 mg/kg Once daily for 30 days G007-LK significantly reduced blood glucose levels and improved glycemic control in diabetic mice. PMC6761205
Mice Lgr5 -EGFP -Ires-CreERT2;R26R -Confetti mice Oral 10 or 50 mg/kg Once daily, for 9 days To assess the effect of G007-LK on duodenal stem cell homeostasis and intestinal epithelium integrity. Results showed that G007-LK inhibited WNT signaling in LGR5+ stem cells and reduced the number and distribution of cells traced from duodenal LGR5+ stem cells, but the morphology of the duodenum remained unchanged, and the mice did not show weight loss or other visible morphological changes. PMC5759193
BALB/c nude mice SW480 and RKO CDX mouse models intraperitoneal injection 20 mg/kg Once daily for 16 days G007-LK failed to restrain tumor growth in SW480 CDX model PMC10793098
mice TG-shApc mouse model intraperitoneal injection 30mg/kg once daily for one week To evaluate the effect of G007-LK on tumors in the TG-shApc mouse model, results showed that G007-LK-treated tumors had reduced BrdU incorporation, loss of Lgr5 expression, and induction of both Krt20 and ALPi. PMC6774804
Mice EGFR mutant PDX model Intraperitoneal 20 mg/kg 5 days a week Combination of G007-LK with osimertinib did not achieve greater tumor growth inhibition than osimertinib monotherapy alone PMC9437746
BALB/c nude mice SW480 and RKO CDX mouse models Intraperitoneal injection 20 mg/kg Once daily for 16 days G007-LK failed to inhibit tumor growth in SW480 and RKO CDX mouse models PMC10793098
SCID mice ALK1510-c4 cells xenograft model Oral 10 mg/kg or 50 mg/kg Once daily for 14 days To evaluate the inhibitory effect of AZ6102 in combination with alectinib on tumor growth. Results showed that the combination significantly suppressed tumor growth. PMC11570601

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.89mL

0.38mL

0.19mL

9.43mL

1.89mL

0.94mL

18.87mL

3.77mL

1.89mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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