Dimitra Papadopoulou, Vasiliki Mavrikaki, Filippos Charalampous, Christos Tzaferis, Martina Samiotaki, Konstantinos D Papavasileiou, Antreas Afantitis, Niki Karagianni, Maria C Denis, Julie Sanchez, Robert Lane, Zacharias Faidon Brotzakis, Georgios Skretas, Dimitris Georgiadis, Alexios N Matralis, George Kollias
Fibroblasts are key regulators of inflammation, fibrosis, and cancer. Targeting their activation in these complex diseases has emerged as a novel strategy to restore tissue homeostasis. Here, we present a multidisciplinary lead discovery approach to identify and optimize small molecule inhibitors of pathogenic fibroblast activation. The study encompasses medicinal chemistry, molecular phenotyping assays, chemoproteomics, bulk RNA-sequencing analysis, target validation experiments and chemical absorption, distribution, metabolism, excretion and toxicity (ADMET)/Pharmacokinetic (PK)/in vivo evaluation...
February 10, 2024: Angewandte Chemie