YONDELIS®

TRABECTEDIN

Yondelis® is a synthetic compound derived from the colonial sea squirt ecteinascidia turbinata.

The original marine source for it is a tunicate with a rounded, leathery body and two short siphons. It lives in shallow waters of around 6 meters on reefs, pilings and other hard surfaces in shallow waters usually on the submerged roots of mangroves. It can be found in the Caribbean Sea and Gulf of Mexico, as well as the Mediterranean Sea, and occasionally as far north as Chesapeake Bay.

The walls of the individual zooids are known as tunics and are strengthened with cellulose, something unusual in animals. They use siphons to connect to their marine environments. The outer siphon surfaces are orange, which is a colorful warning off to potential predators, as well as the sea squirt’s acrid taste.

Ecteinascidia turbinata is a simultaneous hermaphrodite with eggs and sperm being produced by each organism.

After fertilization, the eggs are brooded in the body cavity for about a week. Yondelis® selectively inhibits active transcription of protein-coding genes through binding to promoters and irreversibly stalling elongating RNA polymerase II on the DNA template, thereby leading to double-stranded DNA breaks and apoptosis.

Here’s how it works

Yondelis® has a unique mechanism of action based on interaction with the minor groove of deoxyribonucleic acid (DNA), bending the helix to the major groove. This binding to DNA triggers a cascade of events affecting several transcription factors, DNA binding proteins, and DNA repair pathways, resulting in perturbation of the cell cycle.

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