Fosbretabulin

Fosbretabulin (also known as combretastatin A-4 phosphate or CA4P) is a microtubule destabilizing experimental drug, a type of vascular-targeting agent, a drug designed to damage the vasculature (blood vessels) of cancer tumours causing central necrosis. It is a derivative of combretastatin. It is formulated as the salts fosbretabulin disodium and fosbretabulin tromethamine.[1]

Fosbretabulin
Clinical data
Other namesCombretastatin A-4 phosphate; CA4P; CA4PD; fosbretabulin disodium; fosbretabulin tromethamine
Legal status
Legal status
  • Investigational
Identifiers
IUPAC name
  • Phosphoric acid mono-{2-methoxy-5-[(Z)-2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenyl} ester
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC18H21O8P
Molar mass396.332 g·mol−1
3D model (JSmol)
SMILES
  • O=P(O)(O)Oc1c(OC)ccc(c1)\C=C/c2cc(OC)c(OC)c(OC)c2
InChI
  • InChI=1S/C18H21O8P/c1-22-14-8-7-12(9-15(14)26-27(19,20)21)5-6-13-10-16(23-2)18(25-4)17(11-13)24-3/h5-11H,1-4H3,(H2,19,20,21)/b6-5-
  • Key:WDOGQTQEKVLZIJ-WAYWQWQTSA-N
  (verify)

Fosbretabulin is a prodrug. In vivo, it is dephosphorylated to its active metabolite, combretastatin A-4.[2]

In July 2007, the pharmaceutical company OXiGENE initiated a 180-patient phase III clinical trial of fosbretabulin in combination with carboplatin for the treatment of anaplastic thyroid cancer.[3] There is currently no fully FDA approved treatment for this form of cancer. By 2017, it had completed multiple clinical trials (e.g. for solid tumours,[4] non-small cell lung cancer[5]) with more in progress.[6]

See also
  • Combretastatin, e.g. for the chemical synthesis

References
  1. "A Ph 2 Study to Investigate the Safety and Activity of Fosbretabulin Tromethamine (CA4P) in the Treatment of Well-Differentiated, Low-to-Intermediate-Grade Unresectable, Recurrent or Metastatic PNET or GI-NET Neuroendocrine Tumors/Carcinoid With Elevated Biomarkers". October 31, 2017 – via clinicaltrials.gov.
  2. "Fosbretabulin disodium". www.cancer.gov.
  3. "A Phase II/III Study to Evaluate the Safety and Efficacy of Combretastatin A-4 Phosphate in Combination With Paclitaxel and Carboplatin in Comparison With Paclitaxel and Carboplatin Against Anaplastic Thyroid Carcinoma [FACT]". May 12, 2014 – via clinicaltrials.gov.
  4. "A Randomized Open-Labeled Phase II Study of Combretastatin A-4 Phosphate in Combination With Paclitaxel and Carboplatin to Evaluate the Safety and Efficacy in Subjects With Advanced Imageable Malignancies". October 28, 2011 – via clinicaltrials.gov.
  5. "A Phase II Study to Assess the Safety and Efficacy of the Combination of Carboplatin, Paclitaxel, and Bevacizumab ± Combretastatin A4 Phosphate (CA4P) Followed by Bevacizumab ± CA4P in Subjects With Chemotherapy Naïve Stage IIIB/IV Non-Squamous Cell Histology Non-Small Cell Lung Cancer (NSCLC)". January 22, 2015 – via clinicaltrials.gov.
  6. "Search of: CA4P - List Results - ClinicalTrials.gov". clinicaltrials.gov.


This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.