Drug safety articles from across Nature Portfolio

An analysis of whole-exome sequencing data linked to longitudinal electronic health records from 44,028 British South Asians finds new gene–phenotype associations and identifies 2,991 genes with rare biallelic predicted loss-of-function genotypes.

IMiD-based PROTACs may degrade IKZF1/3 with hematologic effects. This study profiles these liabilities using hematopoietic assays showing stem cell rewiring and interferon activation and introduces a CRBN ligand that reduces them.

Splice-site targeting antisense oligonucleotides can increase the expression of host gene intron-embedded microRNA and affect axonal development in zebrafish.

Complex diseases such as cancer and neurodegeneration involve interconnected biological pathways that limit the effectiveness of single-target therapies. Here, the authors introduce EVOSYNTH, a synthesis-aware multi-target drug discovery framework that integrates latent evolutionary optimization with retrosynthetic prioritization and demonstrates its ability to generate potent and experimentally actionable candidates through representative case studies in Alzheimer’s disease and ovarian cancer.

Zhang et al. introduce FedLG, a federated graph learning framework that leverages Lanczos-based projection to effectively aggregate heterogeneous molecular data. Extensive benchmarks demonstrate its robustness across diverse molecular discovery tasks.

A common side effect of treatment with taxane-based chemotherapy is peripheral neuropathy. Now, Fonseca et al. uncover the endoplasmic reticulum (ER) stress response in leukocytes as the effective mediator of paclitaxel-induced peripheral nerve damage.

Tamoxifen is an essential drug in breast cancer therapy. Unlike prevailing models of therapy-related tumorigenesis, tamoxifen acts by directly activating the PI3K pathway, bypassing the need for mutations in one of the most common driver genes in sporadic uterine cancer. These findings open avenues for investigating similar mechanisms in other drugs.