期刊
BIOORGANIC CHEMISTRY
卷 99, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2020.103866
关键词
c-MYC; G-quadruplex; Melanoma; Imidazole; Benzothiazole
资金
- National Natural Science Foundation of China [81803348, 21672268]
- Natural Science Foundation of Guangdong Province [2018A030310580, 2017B030314030]
- Shenzhen Science and Technology Innovation Commission [JCYJ20170818141916158]
- Guangdong Provincial Key Laboratory of Construction Foundation [2017B030314030]
Aberrant expression of c-MYC oncogene is significantly associated with the occurrence and development of malignant melanoma. Suppression of the c-MYC transcriptional activity accordingly provides a new idea for treating melanoma. Notably, stabilizing the G-quadruplex (G4) structure in the promoter is proved to be effective in downregulating c-MYC transcription. In this work, we developed a drug-like imidazole-benzothiazole conjugate called IZTZ-1, which was confirmed to preferentially stabilize the promoter G4 and thus lower c-MYC expression. Intracellular assays revealed that IZTZ-1 induced cell cycle arrest, apoptosis, thereby inhibiting cell proliferation. Furthermore, IZTZ-1 was demonstrated to effectively inhibit tumor growth in a melanoma mouse model. Consequently, IZTZ-1 showed good potential in the treatment of melanoma. This study provides an alternative strategy to treat melanoma by targeting the c-MYC G4.
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