A drug-like imidazole-benzothiazole conjugate inhibits malignant melanoma by stabilizing the c-MYC G-quadruplex.

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.