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Ref Type Journal Article
PMID (28460359)
Authors Zhang J, Yao D, Jiang Y, Huang J, Yang S, Wang J
Title Synthesis and biological evaluation of benzimidazole derivatives as the G9a Histone Methyltransferase inhibitors that induce autophagy and apoptosis of breast cancer cells.
Journal Vol Issue Date Pages Journal Short Title
Bioorganic chemistry 72 2017 06 168-181 Bioorg Chem
URL
Abstract Text G9a (also known as KMT1C or EHMT2) is initially identified as a H3K9 methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. It is overexpressed in various human cancers and employed as a promising target in cancer therapy. We discovered a benzoxazole scaffold through virtual high-throughput screening, and designed, synthesized 24 derivatives and investigated for inhibition of G9a. After several rounds of kinase and anti-proliferative activity screening, we discovered a potent G9a antagonist (GA001) with an IC50 value of 1.32μM that could induce autophagy via AMPK in MCF7 cells. In addition, we found high concentration of GA001 could induce apoptosis via p21-Bim signal cascades in MCF7 cells. Our results highlight a new approach for the development of a novel drug targeting G9a with a potential to induce autophagy and apoptosis for future breast cancer therapy.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
GA001 GA001 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
GA001 EHMT2 Inhibitor 5 GA001 is an inhibitor of EHMT2 (G9a), which results in upregulation of AMPK activity, subsequently leading to autophagy, and inhibition of cell proliferation and apoptotic induction (PMID: 28460359).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References