| Description |
GNA002 is a potentially and specifically strong EZH2 (Enhancer of zeste homolog 2) inhibitor with an IC50 of 1.1 μM. GNA002 can covalently bind with specific cysteine residue of EZH2 to trigger its ubiquitination and subsequent degradation by the protein quality control E3 ligase, CHIP[1].
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| Related Catalog |
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| Target |
EZH2:1.1 μM (IC50)
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| In Vitro |
GNA002 (10 μM; 72 hours) clearly inhibits the proliferation of numerous cancer cell lines with IC50s of 0.070 μM and 0.103 μM for MV4-11 and RS4-11, especially in cancer cells with relatively increased expression levels of EZH2 mRNA and protein[1]. GNA002 (2 μM; 24 hours) demonstrates an elevated capacity to induce cell death in human cancer cells[1]. GNA002 (0.1-4 μM; 48 hours) efficiently reduces EZH2-mediated H3K27 trimethylation in Cal-27 head and neck cancer cells[1]. Cell Proliferation Assay[1] Cell Line: Numerous cancer cell lines Concentration: 10 μM Incubation Time: 72 hours Result: Inhibited the proliferation of numerous cancer cell lines with IC50s of 0.070 μM and 0.103 μM for MV4-11 and RS4-11. Apoptosis Analysis[1] Cell Line: HN-4 and Cal-27 head and neck cancer cells Concentration: 2 μM Incubation Time: 24 hours Result: Induced cellular apoptosis in human cancer cells. Western Blot Analysis[1] Cell Line: Cal-27 head and neck cancer cells Concentration: 0.1, 0.2, 0.5, 1, 2, 4 μM Incubation Time: 48 hours Result: Reduced H3K27Me3 levels.
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| 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.
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| 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.
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