MLo-1508

MLo-1508 is an experimental small molecule DNA methyltransferase (DNMT) inhibitor being investigated for the treatment of renal cell carcinoma (RCC), including papillary RCC. It functions as an epigenetic modulator by inhibiting the enzymatic activity of DNMT3A and reducing the transcript levels of both DNMT1 and DNMT3A. This action leads to a significant reduction in global DNA methylation, which triggers apoptosis, DNA damage, and cell cycle arrest at the G2/M phase in malignant cells. Preclinical studies have demonstrated that MLo-1508 can sensitize RCC cells to sunitinib treatment, potentially lowering the effective anti-tumoral concentration required and delaying the acquisition of drug resistance. The compound was developed through a collaboration involving the Portuguese Oncology Institute of Porto (IPO Porto), Institut Pasteur, and the French National Centre for Scientific Research (CNRS).