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Development of HDAC Inhibitors Exhibiting Therapeutic Potential in T-Cell Prolymphocytic Leukemia

Krimo Toutah, Nabanita Nawar, Sanna Timonen, Helena Sorger, Yasir S. Raouf, Shazreh Bukhari, Jana von Jan, Aleksandr Ianevski, Justyna M. Gawel, Olasunkanmi O. Olaoye, Mulu Geletu, Ayah Abdeldayem, Johan Israelian, Tudor B. Radu, Abootaleb Sedighi, Muzaffar N. Bhatti, Muhammad Murtaza Hassan, Pimyupa Manaswiyoungkul, Andrew E. Shouksmith, Heidi A. Neubauer, Elvin D. de Araujo, Tero Aittokallio, Oliver H. Krämer, Richard Moriggl, Satu Mustjoki, Marco Herling, Patrick T. Gunning

2021Journal of Medicinal Chemistry46 citationsDOIOpen Access PDF

Abstract

was found to be overexpressed, KT-531 exhibited strong biological responses, and safety in healthy donor samples. Notably, combination studies in T-PLL patient samples demonstrated KT-531 synergizes with approved cancer drugs, bendamustine, idasanutlin, and venetoclax. Our work suggests HDAC inhibition in T-PLL could afford sufficient therapeutic windows to achieve durable remission either as stand-alone or in combination with targeted drugs.

Topics & Concepts

Prolymphocytic leukemiaCancer researchChemistryHDAC6RomidepsinBendamustineCombination therapyBortezomibLeukemiaEpigeneticsPotencyPharmacologyHistone deacetylaseMedicineImmunologyHistoneMultiple myelomaIn vitroChronic lymphocytic leukemiaBiochemistryGeneHistone Deacetylase Inhibitors ResearchProtein Degradation and InhibitorsUbiquitin and proteasome pathways
Development of HDAC Inhibitors Exhibiting Therapeutic Potential in T-Cell Prolymphocytic Leukemia | Litcius