Drug discovery and development articles from across Nature Portfolio

By breaking a clinical candidate into its substructures, fragments with poor bioavailability profiles can be identified, removed and replaced in a compound before entering the laboratory.

Though HER2 (ERBB2) exon 20 insertion mutations occur in ~2% of non-small-cell lung cancers, molecular targeted therapies for such cancers have been lacking. A study now identifies selective HER2 inhibitors that have marked efficacy against tumors driven by HER2 exon 20 insertions, without inhibiting wild-type EGFR activity.

New synthetic methodology enables the formation of a fluorine-substituted benzene bioisostere: strained, saturated bicyclo[1.1.1]pentane.

The organizing principles of click chemistry help scientists make molecules for a variety of applications. Such democratization of synthesis is challenging and rewarding, as useful simplicity is difficult to achieve. We reflect on this and look forward, hoping to continue to tie the joy of functional discovery to the challenges of synthetic chemistry.

Late-stage tritiation with high selectivity, isotopic purity and functional-group tolerance is important for the radiolabelling of drug candidates or bioactive compounds. Now, a broadly applicable protocol using aryl thianthrenium salts allows for tritiation of complex molecules by hydrogenolysis via an intermediate cationic palladium complex.