Drug Discovery And Therapeutic Target Identification
The Drug Discovery Cluster aims to participate in all the stages of early phase drug discovery from chemical biology approaches to new target identification and validation through to the nomination of quality clinical drug candidates to treat human disease of high unmet medical need (e.g. cancer, infection, neurodegenerative disease).
Our work is interdisciplinary, ranging from medicinal and synthetic chemistry to pharmacology, structural biology, proteomics, microbiology and phytomedicines.
The Drug Discovery and Therapeutic Target Identification Cluster is closely aligned with the UCL Translational Research Office which aims to facilitate the translation of basic and clinical research.
People Involved in this Research Theme:
A G-quadruplex-binding compound shows potent activity in human gemcitabine-resistant pancreatic cancer cells
A Mechanochemical Zinc-Mediated Barbier-Type Allylation Reaction under Ball-Milling Conditions
Synthesis and Biological Evaluation of a Novel C8-Pyrrolobenzodiazepine (PBD) Adenosine Conjugate. A Study on the Role of the PBD Ring in the Biological Activity of PBD-Conjugates
Covid 19 Projects
Prof. Shozeb Haider uses computational modelling techniques including molecular dynamics simulations, enhances sampling and deep learning methods to contribute to the understanding the dynamics of SARS-CoV-2 proteins and complexes, the identification of inhibitor binding pockets, and the molecular docking of inhibitors to guide the synthesis of new inhibitor analogues to target Covid-19. For example, providing a dynamic profile for all known inhibitor-binding sites on the nsp15 (Figure 1) to develop pan-β-coronavirus main protease inhibitors. Other projects include computational modelling of a potential binding pocket at the interface between non-structural proteins 10 and 16/14. A current PhD student, Huan Wang is working on modelling Covid-19 proteins.
Figure 1: Overview of ß-coronavirus 3CL Mpro. (A) A phylogenetic tree of the α (blue), ß (yellow), γ (green) and δ (pink) coronavirus family; (B) Structure of the dimeric SARS-CoV2 Mpro enzyme (PDB 6LU7). The two protomers are represented in two different colors; the structural domains in protomer II are illustrated as cartoons; (C) Comparison of SARS-CoV2 (PDB 6LU7, cyan), SARS-CoV (PDB 2C3S, red) and MERS-CoV (PDB 4YLU, green) crystal structures; (D) Sequence alignment between SARS-CoV2 and SARS-CoV highlighting the position of 12 dissimilar residues in yellow. The structural elements have been annotated on the sequence and (E) Spatial position of the dissimilar residues (yellow, SARS-CoV2; green, SARS-CoV) highlighted on the Mpro structure.