The Journey of Bedaquiline: Revolutionizing Tuberculosis Treatment

Tuberculosis (TB) remains a substantial challenge for public health globally, impacting millions of individuals around the world. Despite extensive efforts to control the disease, it continues to pose a major public health challenge, involving therapeutic implications for multi-drug resistant tuberculosis (MDR-TB). Bedaquiline (BDQ), formerly known as TMC207 or R207910, belongs to a class of diarylquinolines (DARQ) that has shown promising therapeutic potential against Mycobacterium tuberculosis (Mtb). Its novel mechanism of action sets it apart from other anti-TB drugs (ATDs), targeting adenosine 5’-triphosphate (ATP) synthase, specifically at the “c” unit. It was approved by the Food and Drug Administration (FDA) in late 2012 for treating adults with MDR-TB when a suitable effective treatment regimen was not readily available. This chapter provides an overview of the global burden of TB, emphasizing an urgent need for innovative solutions due to the rise of drug-resistant TB. It also covers the discovery and early development of BDQ, shedding light on its synthesis, structure-activity relationship (SAR), mechanism of action, pharmacokinetics (PKs), drug metabolism, preclinical and clinical trials, and future concerns to contain the spread of the disease.