Evidence map›Paper›PMID 36355493›Full record

ArticlePharmaceuticals (Basel, Switzerland)2022

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

Harsimran Kaur Garcha, Nabanita Nawar, Helena Sorger, Fettah Erdogan, Myint Myat Khine Aung, Abootaleb Sedighi, Pimyupa Manaswiyoungkul, Hyuk-Soo Seo, Susann Schönefeldt, Daniel Pölöske and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pharmaceuticals (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Harsimran Kaur GarchaDepartment of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada.
Nabanita NawarDepartment of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada.
Helena SorgerInstitute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.ORCID 0000-0002-3380-7770
Fettah ErdoganDepartment of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada.
Myint Myat Khine AungInstitute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.
Abootaleb SedighiDepartment of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada.
Pimyupa ManaswiyoungkulDepartment of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada.
Hyuk-Soo SeoDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Susann SchönefeldtInstitute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.
Daniel PölöskeInstitute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.
Sirano Dhe-PaganonDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Heidi A NeubauerInstitute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.ORCID 0000-0001-7372-7786
Satu M MustjokiTranslational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland.ORCID 0000-0002-0816-8241
Marco HerlingDepartment of Hematology, Cellular Therapy, and Hemostaseology, University of Leipzig, 04109 Leipzig, Germany.
Elvin D de AraujoDepartment of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada.
Richard MorigglInstitute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.ORCID 0000-0003-0918-9463
Patrick T GunningDepartment of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada.

Funding

User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI STEVEN E EALICK · 2018 to 2026
$34.2M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
Austrian Science Fund FWF I 4157Austrian Science Fund FWF I 4218NIGMS NIH HHS P30 GM124165NIH HHS S10 OD021527
6 · The paper itself

Abstract

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.

Indexed as

combination treatmentHDAC6NKTCLsmall molecule inhibitorsynergy

Identifiers

PMID36355493
PMCPMC9692247

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.