Taxane

Taxanes are naturally occurring cytotoxic agents, are substances that inhibit the cell growth and cell division. Chemically include taxanes to the diterpenoids ( diterpenes ). Since the early 1990s, taxanes are used in cancer therapy.

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

History

In the search for natural products for cancer therapy by the U.S. National Cancer Institute ( National Cancer Institute ) in 1962 also made of the bark of the Pacific yew (Taxus brevifolia ) samples in the northwestern United States. In the years to 1966 was at the Research Triangle Institute of North Carolina ( USA) discovered that extracts from the bark of yew trees are effective against several mouse leukemia cells. In 1969 the active ingredient of yew extracts was isolated: paclitaxel. It turned but then discovered that you can win only 350 milligrams of active ingredient from the bark of a full-blown Pacific yew tree, other parts of the tree are drug- free, no other then examined yew contains the active ingredient and the chemical synthesis does not appear to be possible due to the complicated molecular structure. Only in the late 1990s, researchers found the French Institute de Chimie of Substances Naturelles ( Gif- sur -Yvette ) a way for mass production: Could A paclitaxel -related substance (10 -DAB) from the needles of the European yew ( Taxus baccata) be converted into several intermediate steps in paclitaxel. Then, 10-DAB was obtained from the average of yew as required in European parks. Having managed to win paclitaxel directly from yew cell cultures, this production method is the industry standard since 2002.

As a first substance selected from the group of the taxanes paclitaxel was first subjected to a clinical trial in 1983 in terms of its applicability in cancer therapy in humans. In December 1993, was the first approval of paclitaxel under the trade name Taxol in Germany for the treatment of ovarian cancer.

First generation taxane

Looking for other taxanes crystallized - the French Institute of Chemistry of Substances Naturelles - the first time in 1985 from baccatin ( is obtained from the needles of the European yew ( Taxus baccata) won ) synthesized docetaxel out. In October 1995, the first EU -wide approval of docetaxel under the trade name Taxotere for the treatment of breast cancer.

Today, paclitaxel (Taxol ®) and docetaxel are used to treat various cancers.

Second generation taxane

The search for more effective taxanes did not let up, and by the discovery of the Ojima - Holton method has found a way to create from 10 - deacetyl baccatin -III ( 10-DAB-III ) from derivatives of paclitaxel.

In this way, Iwao Ojima and his collaborators found at Stony Brook University, a new class of taxanes, which showed significantly higher activity against cancer cells. These were named Second generation taxanes. An example of a second- generation taxanes SB - T -1214, which is currently in the clinical trial and already shows activity against cancer stem cells.

Operation

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