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Drug Evaluation, Preclinical

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Machine-learning-based quality control of contractility of cultured human-induced pluripotent stem-cell-derived cardiomyocytes.

Biochemical and biophysical research communications
The precise and early assessment of cardiotoxicity is fundamental to bring forward novel drug candidates to the pharmaceutical market and to avoid their withdrawal from the market. Recent preclinical studies have attempted to use human-induced plurip...

Broad-Spectrum Profiling of Drug Safety via Learning Complex Network.

Clinical pharmacology and therapeutics
Drug safety is a severe clinical pharmacology and toxicology problem that has caused immense medical and social burdens every year. Regretfully, a reproducible method to assess drug safety systematically and quantitatively is still missing. In this s...

Discovery of Small-Molecule Activators for Glucose-6-Phosphate Dehydrogenase (G6PD) Using Machine Learning Approaches.

International journal of molecular sciences
Glucose-6-Phosphate Dehydrogenase (G6PD) is a ubiquitous cytoplasmic enzyme converting glucose-6-phosphate into 6-phosphogluconate in the pentose phosphate pathway (PPP). The G6PD deficiency renders the inability to regenerate glutathione due to lack...

Validating the validation: reanalyzing a large-scale comparison of deep learning and machine learning models for bioactivity prediction.

Journal of computer-aided molecular design
Machine learning methods may have the potential to significantly accelerate drug discovery. However, the increasing rate of new methodological approaches being published in the literature raises the fundamental question of how models should be benchm...

Machine Learning Models Based on Molecular Fingerprints and an Extreme Gradient Boosting Method Lead to the Discovery of JAK2 Inhibitors.

Journal of chemical information and modeling
Developing Janus kinase 2 (JAK2) inhibitors has become a significant focus for small-molecule drug discovery programs in recent years because the inhibition of JAK2 may be an effective approach for the treatment of myeloproliferative neoplasm. Here, ...

Development of New Methods Needs Proper Evaluation-Benchmarking Sets for Machine Learning Experiments for Class A GPCRs.

Journal of chemical information and modeling
New computational approaches for virtual screening applications are constantly being developed. However, before a particular tool is used to search for new active compounds, its effectiveness in the type of task must be examined. In this study, we co...

Machine learning for target discovery in drug development.

Current opinion in chemical biology
The discovery of macromolecular targets for bioactive agents is currently a bottleneck for the informed design of chemical probes and drug leads. Typically, activity profiling against genetically manipulated cell lines or chemical proteomics is pursu...

Deep learning enables rapid identification of potent DDR1 kinase inhibitors.

Nature biotechnology
We have developed a deep generative model, generative tensorial reinforcement learning (GENTRL), for de novo small-molecule design. GENTRL optimizes synthetic feasibility, novelty, and biological activity. We used GENTRL to discover potent inhibitors...

Hidden bias in the DUD-E dataset leads to misleading performance of deep learning in structure-based virtual screening.

PloS one
Recently much effort has been invested in using convolutional neural network (CNN) models trained on 3D structural images of protein-ligand complexes to distinguish binding from non-binding ligands for virtual screening. However, the dearth of reliab...