Principal Investigator (PI)
The Foundation is providing £243,321 in support.
Andrew Lim - Phat Voong Vinh
GSK will provide facilities for HTS and compound collections to be screened. In addition, GSK will provide resources in kind for DMPK and safety profiling of the interesting hits identified.
Our ultimate aim is to develop new drugs for the treatment of infections caused by Shigella spp. (a major cause of diarrhea in low-income countries) that work through novel mechanisms of action. Within this open-lab application we aim to carry out the following:
Phenotypic screening against Shigella sonnei and Shigella flexneri 2a using chemically diverse compound libraries under a variety of conditions aiming, where possible, to mimic physiological conditions.
Screening compound libraries against AMR isolates in the presence of antimicrobials to which they are resistant, aiming to identify compounds that restore antimicrobial activity
Compound hits will be validated through assay against panels of clinical isolates, including newly emergent MDR strains.
Validated hits will be profiled in various in vitro DMPK assays, such as solubility and metabolic stability. Preliminary safety assessment in silico and in vitro will be additionally performed, as well as hit expansion.