Chemical–Genetic Profiling of Imidazo[1,2-a]pyridines and -Pyrimidines Reveals Target Pathways Conserved between Yeast and Human Cells

Small molecules have been shown to be potent and selective probes to understand cell physiology. Here, we show that imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrimidines compose a class of compounds that target essential, conserved cellular processes. Using validated chemogenomic assays in Saccharomyces cerevisiae, we discovered that two closely related compounds, an imidazo[1,2-a]pyridine and -pyrimidine that differ by a single atom, have distinctly different mechanisms of action in vivo. 2-phenyl-3-nitroso-imidazo[1,2-a]pyridine was toxic to yeast strains with defects in electron transport and mitochondrial functions and caused mitochondrial fragmentation, suggesting that compound 13 acts by disrupting mitochondria. By contrast, 2-phenyl-3-nitroso-imidazo[1,2-a]pyrimidine acted as a DNA poison, causing damage to the nuclear DNA and inducing mutagenesis. We compared compound 15 to known chemotherapeutics and found resistance required intact DNA repair pathways. Thus, subtle changes in the structure of imidazo-pyridines and -pyrimidines dramatically alter both the intracellular targeting of these compounds and their effects in vivo. Of particular interest, these different modes of action were evident in experiments on human cells, suggesting that chemical–genetic profiles obtained in yeast are recapitulated in cultured cells, indicating that our observations in yeast can: (1) be leveraged to determine mechanism of action in mammalian cells and (2) suggest novel structure–activity relationships

A Europe-wide inventory of citizen-led energy action with data from 29 countries and over 10000 initiatives

Numerous case studies show that citizens engage in various ways in renewable and low carbon energy projects, thereby contributing to the sustainable energy transition. To date, however, a systematic and cross-country database on citizen-led initiatives and projects is lacking. By performing a major compilation and reviewing copious data sources from websites to official registries, we provide a Europe-wide inventory with over 10,000 initiatives and 16,000 production units in 29 countries, focusing on the past 20 years. Our data allow cross-country statistical analysis, supporting the elicitation of empirical insights capable of extending beyond the perspective of single case studies. Our data also align with ongoing efforts to implement two EU Directives that aim at strengthening the active role of citizens in the energy transition. While the focus of our data collection is on Europe, the data and methodology can contribute to the global analysis of citizen-led energy action