Clinical pharmacology articles from across Nature Portfolio

Significant progress has been made in understanding the influence of membrane transporters in drug disposition and response. Here, the International Transporter Consortium provides an update on the current status of membrane transporters in drug development and regulatory requirements, discusses recent scientific advances in the field and highlights future directions and unanswered questions.

The US Food and Drug Administration (FDA) has approved sotagliflozin with a broad heart-failure indication, even in the absence of trial data in patients without diabetes. No one knows what the benefits or risks of inhibiting SGLT1 in the heart might be.

APOL1 risk variants are associated with an increased risk of chronic kidney disease. Findings from a new study demonstrate that a small molecule, inaxaplin, inhibits APOL1 channel function; furthermore, inaxaplin reduced proteinuria in patients with focal segmental glomerulosclerosis and two APOL1 risk variants.

Therapy resistance limits the clinical success of tyrosine kinase inhibitors (TKIs) in ALK-positive non-small cell lung cancer. A study now proposes a framework to identify compound resistance mutations to the lorlatinib TKI and provides structure-based drug design approaches to overcome resistance mediated by ALK(G1202R) or ALK(I1171N/S/T).

Building on previous cardiovascular outcome trials with glucagon-like peptide 1 receptor agonists, the AMPLITUDE-O trial reported significant improvements in major adverse cardiovascular and kidney outcomes with efpeglenatide in type 2 diabetes. A longer-term trial with dose-dependent analysis on kidney outcome components will better define the effects of efpeglenatide in the diabetic kidney.