School of Medical Sciences


Drugs developed at the ACSRC

Topoisomerase inhibitors


amsacrine

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.

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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)

Find out more on DACA (XR-5000)

 

Anti-vascular agents


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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.

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Kinase inhibitors


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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.

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Hypoxia-targeted prodrugs


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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 has recently completed a phase I/II clinical trial in advanced acute myeloid leukaemia and acute lymphocytic leukaemia, through the University of Auckland start-up company Proacta Inc. This study demonstrated responses in some patients, but further clinical development has been suspended until such time as we understand how to identify the patients who will benefit.

 

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SN30000 only

SN30000

SN30000, previously known as CEN-209, is activated selectively in hypoxic cells to generate a reactive free radical that damages DNA. It is an improved analogue of the well-studied benzotrazine di-oxide tirapazamine, has superior ability to penetrate into hypoxic tissue and provides greater tumour selectivity than tirapazamine in preclinical models. SN30000 is currently in preclinical development through Cancer Research UK, and will be evaluated clinically for treatment of hypoxic cancers in combination with chemoradiotherapy.

For more information about the Cancer Research UK, visit the Drug Development Office, Cancer Research UK

 

PR610 only

PR-610

PR610 is a hypoxia-activated irreversible pan-HER inhibitor discovered through the collaborative research of the Translational Theraputics Team and the Next Generation Bioreductive Prodrug Group at the ACSRC. PR610 is the first hypoxia selective multikinase inhibitor (HSMKI) to enter human clinical trials.

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