Vadimezan (also known as or ASA404 and dimethyl

xanthone Xanthone is an organic compound with the molecular formula O 6H4CO. It is a white solid. In 1939, xanthone was introduced as an insecticide and it currently finds uses as Insecticide, ovicide for codling moth eggs and as a larvicide. Xanthone ...

acetic acid or DMXAA) is a tumor-

vascular disrupting agent A vascular-targeting agent (VTA) or vascular disrupting agent (VDA) is a drug designed to damage the vasculature (blood vessels) of cancer tumors causing central necrosis. VTAs can be small-molecule or ligand-based. Small-molecule VTAs include: * ...

(tumor-VDA) that attacks the blood supply of a

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

ous

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

to cause tumor regression.

Clinical trials

Non-small cell lung cancer

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 Sting may refer to: * Stinger or sting, a structure of an animal to inject venom, or the injury produced by a stinger * Irritating hairs or prickles of a stinging plant, or the plant itself Fictional characters and entities * Sting (Middle-eart ...

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 Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

in at least two Phase II trials for advanced

non-small cell lung cancer Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to sm ...

(NSCLC) and showed survival extensions of around 5 months when compared to

alone (14.0 months compared to 8.8 months). ASA404 Vascular Disrupting Agent for Solid Tumours
drugdevelopment-technology.com 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 November 2010, the second trial also gave poor interim results.

Other cancers

Vadimezan has also been studied for the treatment of

prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...

and

HER2 Receptor tyrosine-protein kinase erbB-2 is a protein that in humans is encoded by the ''ERBB2'' gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The human protein is also frequently refer ...

-negative

metastatic Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

History

Vadimezan was discovered by Bruce Baguley and William Denny and their teams at the Auckland Cancer Society Research Centre at the

University of Auckland , mottoeng = By natural ability and hard work , established = 1883; years ago , endowment = NZD $293 million (31 December 2021) , budget = NZD $1.281 billion (31 December 2021) , chancellor = Cecilia Tarrant , vice_chancellor = Dawn F ...

New Zealand New Zealand ( mi, Aotearoa ) is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and over 700 smaller islands. It is the sixth-largest island count ...

. It was licensed to Antisoma in 2001.

Novartis Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...

acquired the worldwide rights for it in 2007 and it underwent

development Development or developing may refer to: Arts *Development hell, when a project is stuck in development *Filmmaking, development phase, including finance and budgeting *Development (music), the process thematic material is reshaped *Photographi ...

by Antisoma and Novartis. 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.

References

{{Reflist, 30em Antineoplastic drugs Experimental cancer drugs Abandoned drugs Xanthones Carboxylic acids