Advancing TET Inhibitor Development: From Structural Insights to Biological Evaluation
Year: 2025
Type: article
Abstract: Ten-eleven translocation (TET) methylcytosine dioxygenases are part of the epigenetic regulatory machinery that erases DNA methylation. Aberrant TET activities are frequently found in hematopoietic malignancies, where loss of TET2 function leads to DNA hypermethylation. A comprehensive understanding of the biological role of TETs is essential to elucidate disease pathogenesis and identify novel therapeutic strategies. We present a robust pipeline integrating protein X-ray crystallography, molecular modeling, and pharmacophore analysis to advance the current TET inhibitor development. In addition, we have synthesized and evaluated a series of 8-hydroxyquinoline (8-HQ) derivatives, demonstrating their potential as chemical tools to explore TET function further. These findings lay the groundwork for a TET-centered therapeutic approach.
Source: ACS Medicinal Chemistry Letters
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: Land Nordrhein-Westfalen, Deutsche Forschungsgemeinschaft, European Synchrotron Radiation Facility, Bundesministerium für Bildung und Forschung, Deutsche Krebshilfe, Mercator Research Center Ruhr, Ministerium für Kultur und Wissenschaft des Landes Nordrhein-Westfalen, European Regional Development Fund
Awards: InCa - Ein systemischer Ansatz zur Untersuchung von heterotypischen Wechselwirkungen von Lungenkrebszellen mit ihrer Mikroumgebung- Chemische Modulation von Kinasen (CheMoKine) zur Aufklärung ihrer Funktion in der Krebsentstehung, - metabolismus und Entzündungsprozessen, G4612700548, G4810103495, G6616697062, G8832781732
OpenAlex ID: W4409261852