G007-LK

A TNKS1/2 inhibitor

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库存: 现货

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5mg

￥987.00

790.00

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25mg

￥2862.00

2290.00

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100mg

￥6225.00

4980.00

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Background

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].

参考文献:
[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.

Protocol

Cell experiment [1]:
Cell lines	COLO-320DM cells lines
Preparation method	The solubility of this compound in DMSO is >26.5mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
Reacting condition	0.2 μmol/L for 7 to 13 days
Applications	G007-LK inhibits cell-cycle progression, reduces colony formation, and induces differentiation, suggesting that b-catenin–dependent maintenance of an undifferentiated state may be blocked by tankyrase inhibition.
Animal experiment [1]:
Animal models	Xenograft COLO-320DM tumors mice
Dosage form	20, 40, 60 mg/kg, IP, daily for 21 days
Application	G007-LK showed antitumor efficacy for Xenograft COLO-320DM tumors mice. TNKS1 and TNKS2 protein levels were reduced, AXIN1 and AXIN2 were stabilized, and b-catenin level was decreased.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
参考文献: [1] Lau T, Chan E, Callow M, Waaler J, et. al. A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth. Cancer Res. 2013 May 15;73(10):3132-44.