F2S4-p-VPA

F2S4-p-VPA is a novel hybrid small molecule composed of a piperidine derivative linked to valproic acid, chemically synthesized to enhance anti-tumor effects. It acts as a VPA derivative containing a tertiary amine pharmacophore reminiscent of methotrexate, aiming to combine beneficial features of both parent components. F2S4-p-VPA has demonstrated cytotoxicity, induction of apoptosis, and cell cycle arrest (in S and G2/M phases) in glioblastoma (LN-18, U373) and triple-negative breast cancer (MDA-MB-231) cell lines, with reduced toxicity toward non-cancerous fibroblasts (3T3-L1). This compound inhibited cancer cell migration more effectively than methotrexate and valproic acid. Its mechanism of inducing apoptosis appears to be Bax/Bak-independent, suggesting a non-canonical pro-apoptotic pathway. F2S4-p-VPA possesses advantageous physicochemical properties compared to methotrexate and valproic acid, making it a promising scaffold for further anti-cancer drug development[1][4][5].