University of Birmingham

Start : October 2016 | Status : Active

The scientist: Dr. Jorge Hernández will focus his research on the optimization of valuable novel Mycobacterium tuberculosis (Mtb) phenotypic active hits with promising developability profile. Jorge is an organic chemist by training and will be working under the supervision of Prof. Gurdyal Besra from the University of Birmingham.

The sponsors: School of Biosciences, University of Birmingham

Foundation funding: The Foundation is providing £102,849 in support, together with co-funding from the European Union FP7 program through its COFUND scheme.

GSK’s contribution: GSK will contribute its extensive medicinal chemistry knowledge in hit-to-lead whole cell programs for TB.

Project Description: Mtb phenotypic high-throughput screening (HTS) represents the main source of new chemical entities (NCE), although a major challenge resides in their successful optimization and mechanism of action (MoA) elucidation. The high level of attrition in early drug discovery stages is often due to the lack of validated hit series with good physicochemical and pharmacokinetic properties. Therefore, selection and optimization of valuable starting points with an understanding of the MoA is extremely crucial. Following recent release of phenotypic confirmed actives from a screening of the GSK library, a selection of 10 starting points, considered tractable and less explored within the TB published chemical space, has been made. The selection was largely based on developability criteria. The first stage of this project will involve an initial prioritization of 3 series which will then be progressed into a more focused hit to lead campaign, to deliver lead candidates with suitable MIC potency and DMPK profile to support evaluation of in vivo efficacy.