Taxanes

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Taxanes are naturally occurring cytostatics , i.e. substances that inhibit cell growth or cell division. Chemically speaking, taxanes belong to the diterpenoids ( diterpenes ). Taxanes have been used in cancer therapy since the early 1990s .

The isoprenoid structure of the taxanes becomes clear in the taxadiene (see picture).

Taxadiene

history

Paclitaxel

In search of natural substances for cancer therapy by the US National Cancer Institute , samples of the bark of Pacific yew trees ( Taxus brevifolia ) were also taken in the northwest of the USA in 1962 . In the years up to 1966 it was discovered at the Research Triangle Institute in North Carolina (USA) that extracts from the yew bark are effective against several mouse leukemia cells. In 1969, the active ingredient in yew extracts was finally isolated: paclitaxel . It then turned out, however, that only 350 milligrams of active ingredient can be obtained from the bark of a fully grown Pacific yew tree, other parts of the tree are free of active ingredients, no other yew species examined contains the active ingredient and chemical synthesis did not seem possible due to the complicated molecular structure. It was not until the end of the 1990s that researchers at the French Institute de Chimie des Substances Naturelles ( Gif-sur-Yvette ) found a way for mass production: A paclitaxel-related substance (10-DAB) made from the needles of the European yew tree ( Taxus baccata ) could be converted into paclitaxel in several intermediate steps. Then 10-DAB was obtained from the cut of yew trees in European parks as required. After it was possible to obtain paclitaxel directly from yew cell cultures , this production method has been the industrial standard since 2002.

As the first substance from the group of taxanes, paclitaxel was first subjected to clinical testing in 1983 with regard to its applicability in cancer therapy in humans. In December 1993, paclitaxel was first approved in Germany under the trade name Taxol for the treatment of ovarian cancer .

First generation taxanes

In the search for other taxanes - in the French Institute de Chimie des Substances Naturelles - docetaxel , first synthesized in 1985 from baccatin (obtained from the needles of the European yew tree ( Taxus baccata )) crystallized out. In October 1995 the first EU-wide approval of docetaxel under the trade name Taxotere for the therapy of breast cancer .

Today, Paclitaxel (brand name Taxol) and Docetaxel are used to treat various cancers.

Second generation taxanes

SB-T-1214

The search for more effective taxanes continued, and with the discovery of the Ojima-Holton process , a way was found to create derivatives of paclitaxel starting from 10-deacetyl-baccatin-III (10-DAB-III) .

In this way, Iwao Ojima and his colleagues at Stony Brook University found a new class of taxanes that were significantly more effective against cancer cells. These were given the name Second Generation Taxanes . An example of a second generation taxane is SB-T-1214 , which is currently in clinical testing and is already showing effects on cancer stem cells .

Mode of action

Taxanes inhibit cell division and thus tumor growth by inhibiting the breakdown of the spindle apparatus , making it unusable for its essential function in mitosis . The microtubules that form the spindle apparatus are essential for the distribution of the duplicated genetic material between the two daughter cells during cell division.

literature

Web links

Individual evidence

  1. ↑ Six trees for a human life. In: Therapy Innovation 7: Individually against the tumor. Published by the Association of Researching Pharmaceutical Companies e. V., Berlin 2006