NK/T-cell lymphoma (NKTCL) and
T-cell non-Hodgkin lymphomas (
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
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
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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:92812 |
| Date | 29 July 2024 |
| Creators | Garcha, Harsimran Kaur, Nawar, Nabanita, Sorger, Helena, Erdogan, Fettah, Aung, Myint Myat Khine, Sedighi, Abootaleb, Manaswiyoungkul, Pimyupa, Seo, Hyuk-Soo, Schönefeldt, Susann, Pölöske, Daniel, Dhe-Paganon, Sirano, Neubauer, Heidi A., Mustjoki, Satu M., Herling, Marco, de Araujo, Elvin D., Moriggl, Richard, Gunning, Patrick T. |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1424-8247, 10.3390/ph15111321 |
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