GNA002

Product NameGNA002
CAS1385035-79-9
MFC42H55NO8
MW701.9
EINECS
MOL File1385035-79-9.mol

Chemical Properties

Boiling point	864.7±65.0 °C(Predicted)
Density	1.22±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	Soluble in DMSO
pka	7.10±0.60(Predicted)
form	Oil
color	Light yellow to yellow

Usage And Synthesis

Description

GNA002 is a highly potent, specific and covalent EZH2 (Enhancer of zeste homolog 2) inhibitor. It can specifically and covalently bind to Cys668 within the EZH2-SET domain, triggering EZH2 degradation through COOH terminus of Hsp70-interacting protein (CHIP)-mediated ubiquitination.

Uses

GNA002 is a highly potent, specific and covalent EZH2 (Enhancer of zeste homolog 2) inhibitor with an IC50 of 1.1 μM. GNA002 can specifically and covalently bind to Cys668 within the EZH2-SET domain, triggering EZH2 degradation through COOH terminus of Hsp70-interacting protein (CHIP)-mediated ubiquitination. GNA002 efficiently reduces EZH2-mediated H3K27 trimethylation, reactivates polycomb repressor complex 2 (PRC2)-silenced tumor suppressor genes[1].

in vivo

GNA002 (oral administration; 100 mg/kg; daily) significantly decreases the volumes of Cal-27-derived tumors and reduces H3K27Me3 levels in tumor tissues. GNA002 also significantly suppresses the in vivo tumor growth derived from the xenografted A549 lung cancer cells, Daudi and Pfeiffer cells. GNA002 inhibits the aberrant oncogenic functions of EZH2, thus inhibiting tumor growth in vivo, at least in the xenograft experimental model^[1].

Animal Model:	Male BALB/C Nude mice aged 30-35 days and weighing 18-22 g, bearing Cal-27 xenograft tumors^[1]
Dosage:	100 mg/kg
Administration:	Oral administration; daily
Result:	Decreased the size and weight of tumors formed by Cal-27 cells.

IC 50

EZH2: 1.1 μM (IC₅₀)

References

[1] Wang X, et al. A covalently bound inhibitor triggers EZH2 degradation through CHIP-mediated ubiquitination. EMBO J. 2017 May, 36(9):1243-1260. DOI:10.15252/embj.201694058

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