Recent Advances and Perspectives of Small Molecule Modulators Targeting DOT1L

. In addition, abnormal expression, mutations, protein interactions, and nonenzymatic functions of DOT1L play important roles in various diseases. Modulators targeting DOT1L have been developed for more than a decade, and compounds such as competitive inhibitors, protein-protein interaction (PPI) inhibitors, and degraders block DOT1L's pathogenic functions through various pharmacological mechanisms. Challenges and opportunities are discussed in this perspective, aiming to provide valuable insights for the future design of DOT1L modulators.