Lead identification begins with the identification of a compound or class of compounds (or extracts in the case of natural products) with the ability to inhibit or kill Mycobacterium tuberculosis while being less toxic or non-toxic for mammalian cells. The process involves multiple steps to assess potency, selective toxicity, anti-microbial spectrum of activity, and stability in the presence of gastric acid and liver enzymes. Compounds with favorable profiles proceed onto evaluations of pharmacokinetics (measuring concentrations in the blood and in the lungs) and the ability to inhibit/kill M. tuberculosis in a living host. A compound that can do the latter is considered to be a lead and efforts are then made to optimize its safety and efficacy through chemical modification. An example of the process is shown below.
