Redox Homeostasis Modulators

Our team has synthesised two series of heterocyclic cyclohexadienones (Quinols), and we have evaluated lead molecules, PMX 464 and PMX 290, from both series.

Model of PMX 464 Bound to Human Thioredoxin

Both compounds have shown potent in vitro and in vivo cytotoxic activity against some of the most common types of human tumour, including colon, breast, renal and melanoma.

We expect a development candidate to enter the clinic by the end of 2008.

Our experimental data suggest that these compounds are able to modulate redox homeostasis in several ways and the wide-ranging anti-tumour activity of these compounds may be due to multiple mechanisms of action, including:

  • Print this page
  • Email this page to a friend

Relevant Publications

External Link Antitumour quinols: Role of glutathione in modulating quinol-induced apoptosis and identification of putative cellular protein targets.
 
External Link Cytotoxic and antiangiogenic activity of AW464 (NSC 706704), a novel thioredoxin inhibitor: an in vitro study.
 
External Link Elucidation of thioredoxin as a molecular target for antitumour quinols.
 
External Link Induction and apoptosis without redox catastrophe by thioredoxin-inhibitory compounds.
 
External Link Novel thioredoxin inhibitors paradoxically increase Hypoxia-inducible factor-α expression but decrease functional transcriptional activity, DNA binding, and degradation.

Additional Bibliography
 
Diagrams
 
Download PDF Model of PMX 464 Bound to Human Thioredoxin
(1,600kb)