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Record W3171699140 · doi:10.1021/acs.jmedchem.1c00420

Development of HDAC Inhibitors Exhibiting Therapeutic Potential in T-Cell Prolymphocytic Leukemia

2021· article· en· W3171699140 on OpenAlexafffund
Krimo Toutah, Nabanita Nawar, Sanna Timonen, Helena Sorger, Yasir S. Raouf, Shazreh Bukhari, Jana von Jan, Aleksandr Ianevski, Justyna M. Gawel, Olasunkanmi O. Olaoye, Mulu Geletu, Ayah Abdeldayem, Johan Israelian, Tudor B. Radu, Abootaleb Sedighi, Muzaffar N. Bhatti, Muhammad Murtaza Hassan, Pimyupa Manaswiyoungkul, Andrew E. Shouksmith, Heidi A. Neubauer, Elvin D. de Araujo, Tero Aittokallio, Oliver H. Krämer, Richard Moriggl, Satu Mustjoki, Marco Herling, Patrick T. Gunning

Bibliographic record

VenueJournal of Medicinal Chemistry · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicHistone Deacetylase Inhibitors Research
Canadian institutionsUniversity of Toronto
FundersH2020 European Research CouncilCanada Research ChairsOntario Ministry of Research, Innovation and ScienceCanadian Cancer Society Research InstituteCanadian Institutes of Health ResearchSyöpäsäätiöAcademy of FinlandHorizon 2020 Framework ProgrammeNatural Sciences and Engineering Research Council of CanadaSyöpäjärjestötAustrian Science FundCanadian Cancer SocietyLeukemia and Lymphoma Society of Canada
KeywordsProlymphocytic leukemiaCancer researchChemistryHDAC6RomidepsinBendamustineCombination therapyBortezomibLeukemiaEpigeneticsPotencyPharmacologyHistone deacetylaseMedicineImmunologyHistoneMultiple myelomaIn vitroChronic lymphocytic leukemiaBiochemistry

Abstract

fetched live from OpenAlex

was found to be overexpressed, KT-531 exhibited strong biological responses, and safety in healthy donor samples. Notably, combination studies in T-PLL patient samples demonstrated KT-531 synergizes with approved cancer drugs, bendamustine, idasanutlin, and venetoclax. Our work suggests HDAC inhibition in T-PLL could afford sufficient therapeutic windows to achieve durable remission either as stand-alone or in combination with targeted drugs.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.624

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.010
GPT teacher head0.260
Teacher spread0.251 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations46
Published2021
Admission routes2
Has abstractyes

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