Investigators at the National Institute of Diabetes and Digestive and Kidney Disorders (NIDDK) have used a gene-constrained analysis to identify nine new Alzheimer’s disease (AD) risk genes that are possibly linked to the higher prevalence of AD in people with African ancestry. One of those genes, GNB5, regulates the stability of certain G protein-signaling proteins, which are activated by G protein-coupled receptors (GPCRs). The authors showed that mice with only one copy of Gnb5 developed more amyloid plaques and tau tangles than those with two copies.

Kupffer cells are macrophages located in the liver that play a key role in liver pathology, concretely in metabolic dysfunction-associated steatotic liver disease (MASLD; formerly nonalcoholic fatty liver disease or NAFLD), but the mechanisms behind this are poorly understood.

Cumulus Oncology Ltd. and Leadxpro AG have signed a research collaboration focused on the discovery and development of small molecules targeting an undisclosed and novel cancer-focused G protein-coupled receptor (GPCR).

Researchers have developed a new highly effective therapeutic for pain relief by altering the chemical properties of an antinausea drug, netupitant. The modified drug is able to enter the intracellular membrane-bound endosome and target the GPCRs therein, rather than at the cell surface, that leads to optimal pain relief. The study, published in the Proceedings of the National Academy of Sciences (PNAS) on May 22, 2023, was led by Nigel Bunnett, Professor and Chair of Molecular Pathobiology at NYU College of Dentistry, and illustrates how GPCR-mediated pain signaling occurs inside the endosomes rather than at the surface, highlighting the need for drugs that can reach receptors within the cells itself.

Confo Therapeutics NV closed out March in much the same way as it began the month – with a deal. 

Confo Therapeutics NV closed out March in much the same way as it began the month – with a deal. The Ghent, Belgium-based company has entered a collaboration agreement with Daiichi Sankyo Co. Ltd. to generate brain-penetrant small-molecule agonists to an undisclosed G protein-coupled receptor (GPCR) implicated in central nervous system diseases.

Psychedelic drugs may exert their effects at intracellular serotonin receptors that serotonin itself, which does not cross cell membranes, cannot reach. The findings were published in the Feb. 17, 2023, issue of Science by researchers from the University of California at Davis.

Certa Therapeutics Pty Ltd. is progressing antifibrotic agent FT-011 to phase III trials following positive results in a phase II trial that showed clinically meaningful improvements for more than 60% of patients with scleroderma in 12 weeks. FT-011 targets a previously undrugged G protein-coupled receptor, and these early efficacy outcomes in scleroderma suggest potential for FT-011 to treat other indications in Certa’s pipeline, including diabetic retinopathy and other forms of chronic kidney disease.

Certa Therapeutics Pty Ltd. is progressing antifibrotic agent FT-011 to phase III trials following positive results in a phase II trial that showed clinically meaningful improvements for more than 60% of patients with scleroderma in 12 weeks. FT-011 targets a previously undrugged G protein-coupled receptor, and these early efficacy outcomes in scleroderma suggest potential for FT-011 to treat other indications in Certa’s pipeline, including diabetic retinopathy and other forms of chronic kidney disease.