In the last few years macrocyclic peptides have emerged as a better class of lead candidates for inhibition of protein-protein interactions with respect to conventional small molecules. The IRBM peptide chemistry team collaborated with the teams at Merck & co. and RaPharma to develop potent macrocyclic peptide inhibitors of PCSK9 a key regulator of plasma LDL-cholesterol.
IRBM & University of Rome publishes in Nature on crucial signaling pathway in muscle homeostasis and regeneration
IRBM, working with the University of Rome’s Department of Biology, examined signaling pathways involved with the regulation of Fibro/Adipogenic Progenitors (FAPs). FAPs are muscle-interstitial progenitors mediating pro-myogenic signals that are critical for muscle homeostasis and regeneration. In myopathies, FAP adipogenesis goes awry, causing fat infiltrates and muscle degeneration. By combining pharmacological screening, high-dimensional mass cytometry and in silico network modelling with the integration of single-cell/bulk RNA sequencing data, the canonical WNT/GSK/β-catenin signaling was highlighted as a crucial pathway modulating FAP adipogenesis triggered by insulin signaling. This suggests FAPs have potential in mediating autocrine/paracrine responses in the muscle niche.