A Short History of Topoisomerases at Actelion Pharmaceuticals

The discovery of novel antibacterials devoid of cross resistance is of utmost importance. At the same time, biological pathways and processes suitable to be targeted are limited. At Actelion Pharmaceuticals we decided to work on novel bacterial topoisomerase inhibitors (NBTI) to discover new antibiotics with broad spectrum activity and limited resistance development for use against severe hospital infections. This paper summarizes the learnings and results of our efforts in the field, which led to the discovery of multiple chemical classes with potent Gram-negative activity and ultimately to the selection of several compounds that underwent preclinical profiling.