Vadimezan
| File:Vadimezan.png | |
| Clinical data | |
|---|---|
| Other names | ASA404, DMXAA |
| ATC code |
|
| Identifiers | |
| |
| CAS Number | |
| ChemSpider | |
| UNII | |
| ChEBI | |
| E number | {{#property:P628}} |
| CompTox Dashboard (EPA) |
|
| ECHA InfoCard | {{#property:P2566}}Lua error in Module:EditAtWikidata at line 29: attempt to index field 'wikibase' (a nil value). |
| Chemical and physical data | |
| Formula | C17H14O4 |
| Molar mass | 282.295 g·mol−1 |
| 3D model (JSmol) | |
| |
| ☒check (what is this?) (verify) | |
Vadimezan (also known as or ASA404[1] and dimethylxanthenone acetic acid or DMXAA) is a tumor-vascular disrupting agent (tumor-VDA) that attacks the blood supply of a cancerous tumor to cause tumor regression.[2]
Clinical trials
[edit | edit source]Non-small cell lung cancer
[edit | edit source]Despite positive results at the preclinical stage, vadimezan failed in human clinical trials. Studies have demonstrated the reason for the inefficacy. Vadimezan was shown to target the STING pathway,[3] however, this effect is mouse specific; it has no effect on human STING.[4] 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.[5]
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).[6] [7] 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.[8] Interim results on another phase III trial as second-line therapy for NSCLC were completed in 2011. In November 2010, the second trial also gave poor interim results.[9]
Other cancers
[edit | edit source]Vadimezan has also been studied for the treatment of prostate cancer[7] and HER2-negative metastatic breast cancer.[1][10]
History
[edit | edit source]Vadimezan 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.[10] It was licensed to Antisoma in 2001. Novartis acquired the worldwide rights for it in 2007 and it underwent development by Antisoma and Novartis.[7][10] In 2020 CRM Therapeutics, a Dutch drug-development company, initiated research for re-developing Vadimezan in combination with its proprietary targeted delivery platform. Since January 2021, Vadimezan is a registered trademark of CRM Therapeutics B.V., Rotterdam.[citation needed]
References
[edit | edit source]- ^ a b Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ ASA404, A Novel Cancer Agent, Begins Pivotal Trial To Explore New Approach In Treating Lung Cancer, The Leading Cause Of Cancer Death Archived 3 January 2009 at the Wayback Machine, Medical News Today, 14 April 2008
- ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ a b c ASA404 Vascular Disrupting Agent for Solid Tumours, drugdevelopment-technology.com
- ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ a b c Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).