G007-LK

• CAT Number: I001470
• CAS Number: 1380672-07-0
• Molecular Formula: C25H16ClN7O3S
• Molecular Weight: 529.959
• Purity: ≥95%
• Target: tankyrase
• Solubility: DMSO: ≥ 30 mg/mL
• Storage: Store at -20°C
• IC50: 46 nM/23 nM (TNKS1/TNKS2)
• IUPAC 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
• InChI: 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+
• InChIKey: HIWVLHPKZNBSBE-OUKQBFOZSA-N
• SMILES: CS(=O)(=O)C1=CN=C(C=C1)C2=NN=C(N2C3=CC=CC=C3Cl)C=CC4=NN=C(O4)C5=CC=C(C=C5)C#N

G007-LK(CAT: I001470) is a selective inhibitor of tankyrase 1 and 2 (TNKS1/2), which are enzymes involved in telomere maintenance and Wnt signaling pathways. By inhibiting TNKS1/2, G007-LK can prevent the degradation of Axin, a key component of the Wnt signaling pathway, leading to inhibition of Wnt signaling and potential anti-tumor effects.

Reference

1:J Med Chem. 2013 Apr 11;56(7):3012-23. doi: 10.1021/jm4000566. Epub 2013 Mar 29. Structural basis and SAR for G007-LK, a lead stage 1,2,4-triazole based specific tankyrase 1/2 inhibitor.Voronkov A,Holsworth DD,Waaler J,Wilson SR,Ekblad B,Perdreau-Dahl H,Dinh H,Drewes G,Hopf C,Morth JP,Krauss S, PMID: 23473363 DOI: 10.1021/jm4000566
Abstract: 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 Å 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.