TN1 is a potent inducer of fetal hemoglobin (HbF).

TN1 demonstrates superior efficacy in inducing fetal hemoglobin (HbF) in KU812 and K562 leukemia cell lines compared to hydroxyurea (HU), promoting HbF protein synthesis in a dose-dependent manner. At a concentration of 100 nM, TN1 significantly enhanced γ-globin expression—2.9-fold in KU812 cells and 3.7-fold in K562 cells—surpassing the enhancement achieved with 50-100 μM HU (1.8- and 1.9-fold increases, respectively), making it more effective than the standard SCD treatment. Remarkably, TN1's EC50 value for HbF induction is vastly lower than HU's (HU: EC50=50-100 μM; TN1: EC50=100 nM), highlighting its potency. Additionally, TN1 outperforms other small-molecule HbF inducers, including sodium butyrate and various histone deacetylase (HDAC) inhibitors. Its efficacy extends to increasing γ-globin mRNA transcription by more than fourfold, affecting both transcriptional and protein levels of γ-globin. Within 24 hours of treatment, an increase in both γ-globin mRNA and protein synthesis is observed. TN1 further triggers β-globin mRNA production alongside γ-globin mRNA, akin to the action of hydroxyurea, presenting a promising therapeutic candidate for further exploration.