HPPD inhibition case study

A problem presented at the UK MMSG Reading 2011.

Presented by:
Dr Pratibha Mistry (Toxiciology, Syngenta)
Dr Domingo Salazar (Product Safety, Syngenta)
Dr Alexander Stevens (Product Metabolism & Analytical Sciences, Syngenta)
Mr Kim Travis (Product Safety, Syngenta)
Dr Russell Viner (Chemistry, Syngenta)

Problem Description

4-hydroxyphenylpyruvate dioxygenase (HPPD) is an enzyme involved in the breakdown of excess tyrosine, an amino acid, in the body of mammals. It is present mainly in the liver. One inhibitor of HPPD is used successfully as a pharmaceutical, where it acts by blocking the tyrosine breakdown pathway. However, the inhibition of HPPD can result in toxicities in some species, especially rats. In plants the same enzyme has a completely different role, being essential for the synthesis of components needed for photosynthesis. The inhibition of HPPD is the mode of action of a number of commercialised herbicides, as this inhibition causes bleaching and ultimately death of the plant.

A variety of in silico, in vitro and in vivo information is now available. The challenge is to suggest ways of making better use of the existing database to assess the potency and safety of new HPPD inhibitors. In particular, to explore the extent to which in silico and in vitro information can be used to predict in vivo outcomes in mammals.

Can the Study Group participants suggest ways of making better use of existing databases on relevant pathways to assess the potency of new HPPD inhibitors. In particlular:

Download the full problem description

Follow-Up Activities

The following follow-up meetings have occured to continue work on aspects of this problem:

2011 HPPD Initiation Follow-up Meeting
Monday 17th October 2011, Jealott's Hill Int. Research Centre