An approachable framework for the scalable implementation of proteome-wide thermal shift assays to assess drug mechanisms of action.

In a drug choice setting, rats’ preference is initially driven by deliberative processes but shifts to more automatic selection processes after extended training, in accordance with the sequential choice model.

Combined analyses of transcriptome and chromatin accessibility elucidated the mechanisms underlying cancer cell lines response to antitumor candidates and provided a versatile perturbation-informed basal signature able to predict drug sensitivity.

A microfluidic device induces doxorubicin-resistant polyaneuploid cancer cells from triple negative breast cancer cells, revealing NUPR1/HDAC11 axis dysfunction drives chemoresistance, increasing tumor heterogeneity and impacting clinical outcomes.

Single-molecule tracking at scale, analyzing millions of cells and thousands of compounds per day, demonstrates that measuring protein motion provides mechanistic insights relevant to drug discovery.

Nearly a thousand diverse adaptive mutants converge into a handful of groups for which fitness responds the same way to environmental change.

Pharmacokinetics, the venerable science that measures the dynamics and concentrations an administered drug attains in organs, has been extended to the subcellular level – organelles – by a generalizable new paradigm.

Mathematical modeling shows how RAF inhibitors can actually activate RAF kinases by stabilizing RAF proteins in the conformation capable of dimerization.

Doxycycline used at a slightly higher concentration kills Plasmodium falciparum malaria parasites with faster, first-cycle activity through a novel organelle-specific mechanism.

A transport mechanism is uncovered in the major drug-efflux system in E. coli involving two remote alternating-access conformational cycles, which could provide the basis for the development of allosteric inhibitors against multidrug resistance.