High Efficacy and Drug Synergy of HDAC6-Selective Inhibitor NN-429 in Natural Killer (NK)/T-Cell Lymphoma.
HDAC6
NKTCL
combination treatment
small molecule inhibitor
synergy
Journal
Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
Titre abrégé: Pharmaceuticals (Basel)
Pays: Switzerland
ID NLM: 101238453
Informations de publication
Date de publication:
26 Oct 2022
26 Oct 2022
Historique:
received:
16
08
2022
revised:
11
10
2022
accepted:
12
10
2022
entrez:
10
11
2022
pubmed:
11
11
2022
medline:
11
11
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36355493
pii: ph15111321
doi: 10.3390/ph15111321
pmc: PMC9692247
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Austrian Science Fund FWF
ID : I 4218
Pays : Austria
Organisme : NIGMS NIH HHS
ID : P30 GM124165
Pays : United States
Organisme : NIH HHS
ID : S10 OD021527
Pays : United States
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