Drug discovery articles from across Nature Portfolio

Recent results from the FLAURA2 and MARIPOSA-2 trials underline the continued role of chemotherapy in the treatment of patients with EGFR-mutated non-small-cell lung cancer in the era of targeted therapies. Herein, we argue that the most appropriate and rational sequence and/or combination of therapies remains a matter of discussion.

To develop covalent inhibitors with high potency and low off-target effects, combinatorial approaches that search for candidates from large libraries are desired. Here, sulfur(VI) fluoride exchange (SuFEx) in vitro selection is established for the evolution of covalent aptamers from trillions of SuFEx-modified oligonucleotides. Through this technique, covalent aptamers with optimally balanced selectivity and reactivity are identified.

Amphotericin B is a clinically vital antifungal drug, but it has high renal toxicity. The compound kills cells by forming sponge-like aggregates on the cell surface that remove molecules called sterols from the cell membrane. High-resolution structures of these sterol sponges guided rational development and synthesis of a new class of antifungals that are better for renal health.

A systemically administered peptide (CARSKNKDC) that homes to injured tissues, has inherent ability to promote wound healing. Here, the authors show that this peptide binds to syndecan-4 and activates ARF6 to trigger re-epithelialisation and the naturally occurring wound repair pathway.

Despite advances in GPCR structures and peptide design, creating high-affinity ligands remains a challenge. Here the authors develop a computational method, successfully identifying peptide-based molecules for KOR: their platform shows promise for streamlined GPCR ligand discovery.

Non-addictive treatments for pain are much needed. Here, the authors identify in vivo active leads for inflammatory pain using large library docking against the EP4 prostaglandin receptor.

In this Comment, Berna Özdemir summarizes the evidence for greater drug toxicity in female patients and emphasizes the need for increased awareness of sex differences at all stages of drug development to establish sex-specific anticancer treatment strategies.

Recent results from the FLAURA2 and MARIPOSA-2 trials underline the continued role of chemotherapy in the treatment of patients with EGFR-mutated non-small-cell lung cancer in the era of targeted therapies. Herein, we argue that the most appropriate and rational sequence and/or combination of therapies remains a matter of discussion.

Medicinal chemist Susan Winks shares how she keeps money flowing at the drug-discovery centre she helps to manage.

In the wake of a stalemate among member states, the European Commission has decided to approve the herbicide’s continued use.