The Drug Discovery and Development (H3-D) platform is focused at delivering drug candidates for clinical development, and becoming Africa’s first integrated drug discovery and development Centre. The Centre aims to bridge the gap between basic and clinical studies by building capabilities required to for drug discovery and development. H3-D integrates medicinal chemistry, biology, pharmacology as well as drug metabolism and pharmacokinetics (DMPK) studies as reflected in the processes of Absorption, Distribution, Metabolism and Excretion (ADME). H3-D also focuses on beneficiation of clinically used drugs, including generic medicines. Drug beneficiation, amongst other things, involves selection of the optimum form of a solid drug candidate for pharmaceutical development and (re)formulation. H3-D follows drug discovery process similar to what exists in pharmaceutical companies and applies the same quality standards and methodologies to find molecules of interest, increase their performance, verify their efficacy and safety and get the data necessary for the regulatory approval of clinical trials.

The Centre’s project portfolio in TB and malaria reflects its intention to make an impact in disease areas of strategic importance to South Africa. H3-D supports drug discovery and development programs across other diseases area where its core competencies and enabling technologies and services are applicable.

H3-D capabilities and core competencies include:

  • Medicinal Chemistry (Hit to Lead and Lead Optimization)
  • In vitro and in vivo Mycobacteriology and Parasitology
  • Biochemistry: Recombinant protein expression, protein isolation and characterisation, and development of enzyme assays for evaluating inhibitor efficacy
  • In vitro and in vivo DMPK (Drug Metabolism and Pharmacokinetics): In vitro ADME, in vivo PK evaluation
  • In vitro metabolite generation using mammalian systems (hepatocytes, microsomes, isolated CYP450s), microbial systems/fungal/bacterial (whole cells, cell lysates, purified enzyme) and bio-engineered systems (bactosomes, bacterial CYP450s)
  • Metabolite identification and scale up by fermentation in bioreactor set ups
  • Development of assays for drugs in blood and serum by LC tandem MS
  • Pharmacology of antimalarial drugs and malaria/HIV drug interactions
  • Preparation and physicochemical characterization of polymorphs, solvates, co-crystals and cyclodextrin inclusion complexes of drug candidates
  • Structural Biology: structure-based drug discovery
  • Computational Chemistry: Virtual Screening and Modeling