ATC code none CAS Number 117570-53-3 ECHA InfoCard 100.107.097 Molar mass 282.29 g/mol ChemSpider ID 110486 | Synonyms ASA404, DMXAA UNII 0829J8133H Formula C17H14O4 ChEBI ID 75934 | |
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Vadimezan or ASA404 (originally DMXAA) is a tumor-vascular disrupting agent (tumor-VDA) that attacks the blood supply of a cancerous tumor to cause tumor regression.
Contents
Non-small cell lung cancer
Despite results at the preclinical stage, Vadimezan failed human clinical trials. Recent studies have demonstrated the reason for the inefficacy. Vadimezan was shown to target the STING pathway, however, this effect is mouse specific; it has no effect on human STING. A single amino acid difference at position 162 (S162A) of the cyclic-dinucleotide-binding site of STING makes mouse STING sensitive to the drug, whereas human STING remains insensitive.
Vadimezan had been studied in combination with chemotherapy in at least two Phase II trials for advanced non-small cell lung cancer (NSCLC) and showed survival extensions of around 5 months when compared to chemotherapy alone (14.0 months compared to 8.8 months). In April 2008, a Phase III trial started. In March 2010 the phase III trial of use as a first line therapy for NSCLC gave poor results. Interim results on another phase III trial as second-line therapy for NSCLC were completed in 2011. In Nov 2010 the 2nd trial also gave poor interim results.
Other cancers
As of February 2009 it was being studied for the treatment of prostate cancer and HER2-negative metastatic breast cancer.
History
ASA404 was discovered by Bruce Baguley and William Denny and their teams at the Auckland Cancer Society Research Centre at the University of Auckland in New Zealand. It was licensed to Antisoma in 2001. Novartis acquired the worldwide rights for it in 2007 and it underwent development by Antisoma and Novartis.