TBD-UK Drug Discovery and Development Blueprint

A new TB drug? A novel synthesised compound, dissolved in solvent, awaits assessment against drug resistant strains of Mycobacterium tuberculosis.

From plants to patients.......... Scientists skilled in identifying biologically active components of plants are known as phytochemists. They dry, grind, extract and analyse plant material before assessing it against Mycobacterium tuberculosis to identify potential drug compounds.

What's in a mixture..? Phytochemists can analyse the various chemical components in a biologically active plant extract in many ways. There can be thin layer chromatography plates (TLC) with bands of material stretching out and containing the different chemical ingredients of the mixture.

The cleaner, the better! After TLC analysis, the phytochemist cleans the mixture by flash column chromatography. Here the different compounds can be separated, collected and individually assessed against Mycobacterium tuberculosis to identify exactly which parts of the plant material may contain potential new drug compounds.

A medicinal chemist prepares a silica flash column to purify the compound he has just prepared.

Now the compound is pure it can be evaluated against M. tuberculosis.

A series of compounds are assessed at different concentrations to see how well they kill the mycobacteria. The more potent the compound is the weaker the concentration of drug required.

Specialised software is used to simulate how a compound might interact with a biological enzyme known to be involved in helping the mycobacteria grow and survive. Molecular modellers use this technique as a tool to aid the medicinal chemists design more potent compounds against the enzyme.

TBD-UK Drug Discovery and Development Blueprint

In January 2010, TBD-UK hosted its first conference which brought together 50 prominent UK scientists. As a result of the discussions at this conference, the TBD-UK Drug Discovery and Development Blueprint was originated by Dr Geoff Coxon and further established and developed by the members of TBD-UK. This document underpins UK TB Research and has the models identified and research groups in place to utilise this work. A copy of the blueprint can be viewed via by clicking on the right hand submenu.

Most recently, the Blueprint has been used to progress and drive the ATC (2-Aminothiazole-4-carboxylates) research project and we have just received notification that our outline application to the Medical Research Council Developmental Pathway Funding Scheme has been accepted. A full DPFS application was submitted in March 2011 and we are now awaiting notification of whether this has been successful. This is an exciting development and the TBD-UK blueprint is key to the success of the project. Further details regarding the ATCs can be viewed within Dr Coxon's British Science Festival presentation.

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