*Phenotypic-Screening E*ff*orts at AstraZeneca India*

The continued success of phenotypic screening as a viable alternative to discover novel inhibitors of MTB was based on its ability to circumvent the failure to convert enzyme inhibition into antibacterial activity. The advent of 'rapid sequencing technology' provided an impetus to this approach because of the ability to rapidly sequence the genome to elucidate mechanism of action. This led AZ India to focus on phenotypic screening for lead generation. A diversity library of 100,000 compounds was assembled and used for screening directly against both *M. smegmatis* or *Mycobacterium bovis* BCG cells as surrogates for MTB. Several novel scaffolds and their cognate targets were identified, confirming the validity of this approach; a short list of the results obtained is shown in Table 3. Many of the novel scaffolds identified were found to target DprE1 or the ATP synthase in target enzyme assays.


**Table 3.** Phenotypic screening-based efforts at AstraZeneca India (AZI).
