التفاصيل البيبلوغرافية
| العنوان: |
Development of HDAC Inhibitors Exhibiting Therapeutic Potential in T‑Cell Prolymphocytic Leukemia |
| المؤلفون: |
Krimo Toutah (9214896), Nabanita Nawar (8200374), Sanna Timonen (4336672), Helena Sorger (10942366), Yasir S. Raouf (6430028), Shazreh Bukhari (5693024), Jana von Jan (10942369), Aleksandr Ianevski (7461887), Justyna M. Gawel (6430025), Olasunkanmi O. Olaoye (8200389), Mulu Geletu (1343361), Ayah Abdeldayem (10131951), Johan Israelian (9193629), Tudor B. Radu (9214893), Abootaleb Sedighi (1449262), Muzaffar N. Bhatti (10942372), Muhammad Murtaza Hassan (10131954), Pimyupa Manaswiyoungkul (8200386), Andrew E. Shouksmith (1660915), Heidi A. Neubauer (10942378), Elvin D. de Araujo (8200395), Tero Aittokallio (61010), Oliver H. Krämer (5071706), Richard Moriggl (596825), Satu Mustjoki (210642), Marco Herling (2259418), Patrick T. Gunning (545679) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biophysics, Biochemistry, Medicine, Cell Biology, Genetics, Molecular Biology, Pharmacology, Cancer, Hematology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, KT -531, nontransformed cell lines, hematological cancers, HDAC 6, T-cell prolymphocytic leukemia, HDAC Inhibitors Exhibiting Therapeutic, SAR, T-PLL patient samples, KT -531 synergizes, T-PLL patient cells |
| الوصف: |
Epigenetic targeting has emerged as an efficacious therapy for hematological cancers. The rare and incurable T-cell prolymphocytic leukemia (T-PLL) is known for its aggressive clinical course. Current epigenetic agents such as histone deacetylase (HDAC) inhibitors are increasingly used for targeted therapy. Through a structure–activity relationship (SAR) study, we developed an HDAC6 inhibitor KT-531, which exhibited higher potency in T-PLL compared to other hematological cancers. KT-531 displayed strong HDAC6 inhibitory potency and selectivity, on-target biological activity, and a safe therapeutic window in nontransformed cell lines. In primary T-PLL patient cells, where HDAC6 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. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/journal_contribution/Development_of_HDAC_Inhibitors_Exhibiting_Therapeutic_Potential_in_T_Cell_Prolymphocytic_Leukemia/14751136 |
| DOI: |
10.1021/acs.jmedchem.1c00420.s001 |
| الاتاحة: |
https://doi.org/10.1021/acs.jmedchem.1c00420.s001 |
| Rights: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.F68AE239 |
| قاعدة البيانات: |
BASE |