دورية أكاديمية
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High Efficacy and Drug Synergy of HDAC6-Selective Inhibitor NN-429 in Natural Killer (NK)/T-Cell Lymphoma.

التفاصيل البيبلوغرافية
العنوان: High Efficacy and Drug Synergy of HDAC6-Selective Inhibitor NN-429 in Natural Killer (NK)/T-Cell Lymphoma.
المؤلفون: Garcha HK; Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada.; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6, Canada., Nawar N; Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada.; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6, Canada., Sorger H; Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria., Erdogan F; Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada.; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6, Canada., Aung MMK; Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria., Sedighi A; Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada., Manaswiyoungkul P; Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada.; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6, Canada., Seo HS; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA., Schönefeldt S; Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria., Pölöske D; Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria., Dhe-Paganon S; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA., Neubauer HA; Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria., Mustjoki SM; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland.; Hematology Research Unit, Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, 00014 Helsinki, Finland., Herling M; Department of Hematology, Cellular Therapy, and Hemostaseology, University of Leipzig, 04109 Leipzig, Germany., de Araujo ED; Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada., Moriggl R; Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria., Gunning PT; Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada.; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6, Canada.
المصدر: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2022 Oct 26; Vol. 15 (11). Date of Electronic Publication: 2022 Oct 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101238453 Publication Model: Electronic Cited Medium: Print ISSN: 1424-8247 (Print) Linking ISSN: 14248247 NLM ISO Abbreviation: Pharmaceuticals (Basel) Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, c2004-
مستخلص: 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.
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معلومات مُعتمدة: I 4157 Austria FWF_ Austrian Science Fund FWF; I 4218 Austria FWF_ Austrian Science Fund FWF; P30 GM124165 United States GM NIGMS NIH HHS; S10 OD021527 United States OD NIH HHS
فهرسة مساهمة: Keywords: HDAC6; NKTCL; combination treatment; small molecule inhibitor; synergy
تواريخ الأحداث: Date Created: 20221110 Latest Revision: 20240327
رمز التحديث: 20240327
مُعرف محوري في PubMed: PMC9692247
DOI: 10.3390/ph15111321
PMID: 36355493
قاعدة البيانات: MEDLINE
الوصف
تدمد:1424-8247
DOI:10.3390/ph15111321