Non-tuberculous mycobacteria (NTMs) are emerging as important pathogens in lung infections, especially affecting cystic fibrosis (CF) adults. Among the subspecies of NTM, Mycobacterium abscessus (Mab) is known as the most widespread and worrying pathogen all over the world, displaying resistance to many drugs. There is indeed an urgent need for new drugs against Mab. This study will extend the results of the FFC#19/2018 project, thanks to the collaboration between S. Raffaele Institute in Milan and the University of Moscow, and a new contribution from the University of Zaragoza. The researchers intend to deepen the study of some compounds they have already identified and others to be synthetized. The experiments will evaluate the compounds’ mechanism of action and their drug resistance’ induction, as well as the in vitro activity against Mab biofilm and possible synergistic behavior with currently available drugs. The best compounds will be further characterized (e.g. in combination with CFTR modulators both in vitro and in vivo) and will be tested in vivo in a Mab-infected CF mouse model, with the ultimate goal of finding more effective weapons against M. abscessus and others NTM.