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Record W4392597434 · doi:10.1080/17460441.2024.2322990

Molecular hybridization: a powerful tool for multitarget drug discovery

2024· article· en· W4392597434 on OpenAlexfundno aff
Pedro de Sena Murteira Pinheiro, Lucas Silva Franco, Tadeu L. Montagnoli, Carlos Alberto Manssour Fraga

Bibliographic record

VenueExpert Opinion on Drug Discovery · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicHistone Deacetylase Inhibitors Research
Canadian institutionsnot available
FundersInstituto Nacional de Ciência e Tecnologia de Fármacos e MedicamentosMinistry of Health, British ColumbiaFundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de JaneiroConselho Nacional de Desenvolvimento Científico e Tecnológico
KeywordsDrug discoveryPharmacophoreComputational biologyDiseaseBiologyDrugBioinformaticsNeuroscienceMedicinePharmacologyPathology

Abstract

fetched live from OpenAlex

INTRODUCTION: The current drug discovery paradigm of 'one drug, multiple targets' has gained attention from both the academic medicinal chemistry community and the pharmaceutical industry. This is in response to the urgent need for effective agents to treat multifactorial chronic diseases. The molecular hybridization strategy is a useful tool that has been widely explored, particularly in the last two decades, for the design of multi-target drugs. AREAS COVERED: This review examines the current state of molecular hybridization in guiding the discovery of multitarget small molecules. The article discusses the design strategies and target selection for a multitarget polypharmacology approach to treat various diseases, including cancer, Alzheimer's disease, cardiac arrhythmia, endometriosis, and inflammatory diseases. EXPERT OPINION: Although the examples discussed highlight the importance of molecular hybridization for the discovery of multitarget bioactive compounds, it is notorious that the literature has focused on specific classes of targets. This may be due to a deep understanding of the pharmacophore features required for target binding, making targets such as histone deacetylases and cholinesterases frequent starting points. However, it is important to encourage the scientific community to explore diverse combinations of targets using the molecular hybridization strategy.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.062
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
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 head0.308
Teacher spread0.298 · 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.

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

Citations155
Published2024
Admission routes1
Has abstractyes

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