| Autor: |
Harsimran Kaur Garcha, Nabanita Nawar, Helena Sorger, Fettah Erdogan, Myint Myat Khine Aung, Abootaleb Sedighi, Pimyupa Manaswiyoungkul, Hyuk-Soo Seo, Susann Schönefeldt, Daniel Pölöske, Sirano Dhe-Paganon, Heidi A. Neubauer, Satu M. Mustjoki, Marco Herling, Elvin D. de Araujo, Richard Moriggl, Patrick T. Gunning |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Pharmaceuticals, Vol 15, Iss 11, p 1321 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1424-8247 |
| DOI: |
10.3390/ph15111321 |
| Popis: |
NK/T-cell lymphoma (NKTCL) and γδ T-cell non-Hodgkin lymphomas (γδ T-NHL) are highly aggressive lymphomas that lack rationally designed therapies and rely on repurposed chemotherapeutics from other hematological cancers. Histone deacetylases (HDACs) have been targeted in a range of malignancies, including T-cell lymphomas. This study represents exploratory findings of HDAC6 inhibition in NKTCL and γδ T-NHL through a second-generation inhibitor NN-429. With nanomolar in vitro HDAC6 potency and high in vitro and in cellulo selectivity for HDAC6, NN-429 also exhibited long residence time and improved pharmacokinetic properties in contrast to older generation inhibitors. Following unique selective cytotoxicity towards γδ T-NHL and NKTCL, NN-429 demonstrated a synergistic relationship with the clinical agent etoposide and potential synergies with doxorubicin, cytarabine, and SNS-032 in these disease models, opening an avenue for combination treatment strategies. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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