Catello Giordano Catello Giordano Jonatan Kendler Jonatan Kendler Maximilian Sexl Maximilian Sexl Sebastian Kollman Sebastian Kollman Maxim Varenicja Maxim Varenicja Boglárka Szabó Boglárka Szabó Gerald Timelthaler Gerald Timelthaler Dominik Kirchhofer Dominik Kirchhofer Oldamur Hollóczki Oldamur Hollóczki Suzanne D. Turner Suzanne D. Turner Richard Moriggl Richard Moriggl Lukas Kenner Lukas Kenner Mohamed Touaibia Mohamed Touaibia Olaf Merkel Olaf Merkel Elsevier 2025 Anaplastic Large Cell Lymphoma (ALCL) is an aggressive T-cell lymphoma affecting children and young adults. About 30% of patients develop therapy resistance therefore new precision medicine drugs are highly warranted. Multiple rounds of structure-activity optimization of Caffeic Acid Phenethyl Ester have resulted in CM14. CM14 causes upregulation of genes involved in oxidative stress response and downregulation of DNA replication genes leading to G2/M arrest and subsequent apoptosis induction. In accordance with this, an unbiased proteomics approach, confocal microscopy and molecular modeling showed that TUBGCP2, member of the centrosomal ?-TuRC complex, is a direct interaction partner of CM14. CM14 overcomes ALK inhibitor resistance in ALCL and is also active in T-cell Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia. Interestingly, CM14 also induced cell death in docetaxel-resistant prostate cancer cells thus suggesting an unexpected role in solid cancers. Thus, we synthesized and thoroughly characterized a novel TUBGCP2 targeting drug that is active in ALCL but has also potential for other malignancies. PDFDocument eng 2025-04-10T09:21:12.138540Z 2025 Humans Caffeic Acids Pharmacology Caffeic Acids Chemistry Phenylethyl Alcohol Analogs & Derivatives Phenylethyl Alcohol Pharmacology Phenylethyl Alcohol Chemistry Centrosome Drug Effects Centrosome Metabolism Antineoplastic Agents Pharmacology Antineoplastic Agents Chemistry Apoptosis Drug Effects Cell Line, Tumor Cell Proliferation Drug Effects 5814275 b application/pdf http://creativecommons.org/licenses/by/4.0/