School of Medical Sciences Drugs developed at the ACSRC

Topoisomerase inhibitors

Amsacrine

The anti-leukaemia drug Amsacrine was the first synthetic topoisomerase II inhibitor to be successfully trialled. Clinical trials began in 1978, and in 1983 it became available for the clinical treatment of leukaemia in adults.

Amsacrine

Three further topoisomerase inhibitors have been developed to clinical trial since then by the ACSRC, in collaboration with various partners: Asulacrine (Sparta Pharmaceuticals Inc), DACA (XR-5000) (Xenova Ltd) and XR-11576 (Xenova Ltd) and MLN-944 (Millennium Pharmaceuticals Ltd)

DACA (XR-5000)

Anti-vascular agents

Vadimezan (DMXAA)

DMXAA is a drug that targets and disrupts the immature vasculature of solid tumours, limiting their blood supply and thus their survival. It was initially trialled at Auckland Hospital, New Zealand in 2000 and was partnered with the UK company Antisoma in 2001. Phase II trials were conducted by Antisoma in NZ and Europe. These trials showed that addition of DMXAA to standard drug therapies resulted in higher response rates and substantially longer survival times for patients with non-small cell lung cancer and prostate cancer. Antisoma on-licensed the drug to Novartis in 2007, and they are currently carrying out world-wide Phase III trials in non-small-cell lung cancer. The first patients in these trials were enrolled in Auckland in May 2008.

DMXAA

Antisoma

Kinase inhibitors

Canertinib (CI-1033)

Canertinib (CI-1033) is an inhibitor of the epidermal growth factor receptor tyrosine kinase and was the first irreversible kinase inhibitor to enter clinical trial. This drug entered clinical trial in the US in 2000 and was developed in collaboration with Pfizer (Ann Arbor, USA). Development of canertinib was stopped at the end of Phase II, due to thrombocytopenia, but the drug has become a template for further development. Four analogues, from different companies, are currently in various stages of clinical trial.

Canertinib (CI-1033)

Pfizer

Hypoxia-targeted prodrugs

PR-104

PR-104 is a bioreductive prodrug that is activated to a toxic DNA cross-linking agent (aniline mustard) in the hypoxic (oxygen-deprived) areas of tumours. It is currently in Phase II clinical trial in non-small-cell lung cancer with The University of Auckland start-up company, San Diego based Proacta.

PR-104

Proacta