Trabectedin

Trabectedin

Clinical data
[[Regulation of therapeutic goods |Template:Engvar data]]	EU EMA: by INN
Routes of administration	Intravenous
ATC code	L01CX01 (WHO)
Pharmacokinetic data
Bioavailability	Not applicable (IV only)
Protein binding	94 to 98%
Metabolism	Hepatic (mostly CYP3A4-mediated)
Elimination half-life	180 hours (mean)
Excretion	Mostly fecal
Identifiers
IUPAC name (1'R,6R,6aR,7R,13S,14S,16R)-6',8,14-trihydroxy- 7',9-dimethoxy-4,10,23-trimethyl-19-oxo-3',4',6,7, 12,13,14,16-octahydrospiro[6,16-(epithiopropano oxymethano)-7,13-imino-6aH-1,3-dioxolo[7,8]isoquino [3,2-b][3]benzazocine-20,1'(2'H)-isoquinolin]-5-yl acetate
CAS Number	114899-77-3
PubChem CID	108150
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C39H43N3O11S
Molar mass	761.84 g/mol

WikiDoc Resources for Trabectedin
Articles
Most recent articles on Trabectedin Most cited articles on Trabectedin Review articles on Trabectedin Articles on Trabectedin in N Eng J Med, Lancet, BMJ
Media
Powerpoint slides on Trabectedin Images of Trabectedin Photos of Trabectedin Podcasts & MP3s on Trabectedin Videos on Trabectedin
Evidence Based Medicine
Cochrane Collaboration on Trabectedin Bandolier on Trabectedin TRIP on Trabectedin
Clinical Trials
Ongoing Trials on Trabectedin at Clinical Trials.gov Trial results on Trabectedin Clinical Trials on Trabectedin at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on Trabectedin NICE Guidance on Trabectedin NHS PRODIGY Guidance FDA on Trabectedin CDC on Trabectedin
Books
Books on Trabectedin
News
Trabectedin in the news Be alerted to news on Trabectedin News trends on Trabectedin
Commentary
Blogs on Trabectedin
Definitions
Definitions of Trabectedin
Patient Resources / Community
Patient resources on Trabectedin Discussion groups on Trabectedin Patient Handouts on Trabectedin Directions to Hospitals Treating Trabectedin Risk calculators and risk factors for Trabectedin
Healthcare Provider Resources
Symptoms of Trabectedin Causes & Risk Factors for Trabectedin Diagnostic studies for Trabectedin Treatment of Trabectedin
Continuing Medical Education (CME)
CME Programs on Trabectedin
International
Trabectedin en Espanol Trabectedin en Francais
Business
Trabectedin in the Marketplace Patents on Trabectedin
Experimental / Informatics
List of terms related to Trabectedin

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Please Join in Editing This Page and Apply to be an Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [3] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.

Overview

Trabectedin (also known as ecteinascidin 743 or by the brand name Yondelis) is an experimental anti-tumor drug. First isolated from aqueous ethanol extract of tunicates in 1969, the complex molecule was found to have impressive cytotoxic activities in the pico- to nanomolar range. It is composed of 3 tetrahydroquinoline moieties, 8 rings including one 10-membered heteocyclic ring containing a cystine residue, and 7 chiral centers. This structure was not determined until 1984, and was first totally synthesized by Elias James Corey in 1996.

Synthesis

Biosynthesis is also beleieved to involve the dimerization of two tyrosine residues to form the pentacyclic core of the molecule. The total synthesis by E.J. Corey used this proposed biosynthesis in their attempt at the compounds synthetic creation. Their synthesis utilized such reactions as the Mannich reaction, Pictet-Spengler reaction, the Curtius rearrangement, and chiral rhodium-based diphosphine catalized enantioselective hydrogenation. A separate synthetic process also involved the Ugi reaction to assist in the formation of the pentacyclic core. This reaction was unprecedented for using such a one pot multi-component reaction in the synthesis of such a complex molecule.

Mechanism of action

The biological mechanism of action is believed to involve the production of superoxide near the DNA strand, resulting in DNA backbone cleavage and cell apoptosis. The actual mechanism is not yet known, but is believed to proceed from reduction of molecular oxygen into superoxide via an unusual auto-redox reaction on a hydroxyquinone moiety of the compound following. There is also some speculation the compound becomes 'activated' into its reactive oxazolidine form.

External links

• Yondelis

Template:WikiDoc Sources