GRADE & PURITY 10mM in DMSO

Synonyms

(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

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

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

G007-LK reduces Wnt/β-catenin signaling by preventing poly(ADP-ribosyl)ation-dependent AXIN degradation, thereby promoting β-catenin destabilization. G007-LK completely blocks ligand-driven Wnt/β-catenin signaling in cell culture and display approximately 50% inhibition of APC mutation–driven signaling in most CRC cell lines. G007-LK (0.2 μM) reduces the number of COLO-320DM cells in mitosis from 24% to 12% and decreases HCT-15 cells in S-phase from 28% to 18%. G007-LK suppresses colony formation in CRC lines COLO-320DM and SW403. G007-LK suppresses organoids growth with IC50 of 80 nM.

In vivo

G007-LK exhibits antitumor efficacy in xenograft and genetically engineered CRC models. In the COLO-320DM model, G007-LK reduces tankyrases 1 and tankyrases 2 protein levels, stabilizes AXIN1 and AXIN2, and decreases β-catenin level. Wnt/β-catenin signaling is clearly inhibited in a dose-dependent manner in the efficacy study tumors as indicated by reduced expression of β-catenin–activated genes NKD1, APCDD1, and TNFRSF19 (TROY), as well as increased expression of β-catenin–repressed gene CLIC3. G007-LK treatment increases expression of KRT20 and TM4SF4 in COLO-320DM tumors. G007-LK (20 mg/kg twice daily) achieves 61% tumor growth inhibition. G007-LK reduces Wnt/β-catenin signaling and cell proliferation in normal intestine.
Cell Data

cell lines：

Concentrations：~0.2 μM

Incubation Time：7 to 13 days

Powder Purity:≥97%

Specifications

Synonyms

(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

Specifications & Purity

10mM in DMSO

Biochemical and Physiological Mechanisms

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

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

This product requires cold chain shipping. Ground and other economy services are not available.

Action Type

INHIBITOR

Product Properties

• ALogP: 4.347
• hba_count: 8
• Rotatable Bond: 6

Names and Identifiers

• Isomeric 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
• Molecular Weight: 529.96
• Reaxy-Rn: 22641474
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=22641474&ln=

Associated Targets(Human)

TNKS Tchem Tankyrase-1 (3 Activities)

Discover Target: TNKS

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

TNKS2 Tchem Tankyrase-2 (3 Activities)

Discover Target: TNKS2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

Chemical and Physical Properties

• DMSO(mg / mL) Max Solubility: 100
• DMSO(mM) Max Solubility: 188.6934863
• Water(mg / mL) Max Solubility: ＜1