Scientists also isolated this compound from Taxus Pacific and found that it has a wide range of anti-malignant effects. Because of children
Paclitaxel can be decomposed into two crystallizable parts by Zemplen alcoholysis. 1970, these two triangle institutes studied science.
Scientists confirmed its structure by X-ray diffraction analysis, and published this research result in 197 1. Taxol molecule is one of them.
An extremely complex tetracyclic diterpene compound: a taxane ring plus an alkoxy ring composed of four elements, in C-2 and C.
-13 also has phenoxy and ester side chains, respectively.
Although paclitaxel shows strong cytotoxicity to malignant tumors in tissue culture and several malignant tumor cell lines.
Sex, but it has not attracted enough attention in the past ten years after it was discovered. There are two main reasons for this:
First of all, its resources are extremely limited; Secondly, its water solubility is poor. Water solubility is very important for anticancer drugs, but violet
Paclitaxel is almost insoluble in water (the maximum solubility is about 20mg/L). At the same time, Wall and Vanni continue to heat up.
The broad-spectrum anticancer activity of paclitaxel they found was studied. 1979, Susan from Albert Einstein College of Medicine.
Horwitz reported the unique mechanism of action of paclitaxel, which made it the embryonic form of a new class of tumor chemotherapy drugs.
Stage.
In fact, tubulin, which is closely related to cell mitosis, exists almost universally in all eukaryotic cells. Microtubule protein component
In mammals, there are at least six kinds of α -tubulin and the corresponding same amount of β -tubulin.
Protein, each tubulin is encoded by a different gene. These different types of tubulin are very similar. They
Can be reversibly polymerized into microtubules. Chromosome separation needs the help of these microtubules. After mitosis, these microtubules dissolve again.
Aggregation into tubulin. Short-term disintegration of hammer microtubules can give priority to killing abnormally divided cells, some important anticancer drugs.
Such as colchicine, vinblastine, vincristine, etc. It works by preventing tubulin from re-polymerizing. With these resistances,
In contrast to mitotic drugs, paclitaxel is the first drug known to interact with tubulin polymers, which can
Closely combine with microtubules and stabilize them. And paclitaxel-promoted tubulin can be used without GTP (usually
GTP is needed to polymerize tubulin into microtubules. Conducive to the depolymerization of tubulin
Under the conditions of low temperature, calcium ion and dialysis, the tubulin polymer formed by paclitaxel is still stable.
Compared with α, β-tubulin dimer, from the chemical calculation, paclitaxel only reacts with one of α, β-tubulin.
A special combination of reversibility. However, studies have shown that when the concentration is nanomole, paclitaxel shows the same concentration as paclitaxel.
Colchicine, Catharanthus alkaloids and other similar effects, that is, by preventing tubulin from polymerizing into microtubules.
In addition, paclitaxel can also induce the formation of specific tubulin bundles in cells.
The success of the above research rekindled people's enthusiasm for further research and development of paclitaxel. Meanwhile, the National Cancer Institute
The institute has obtained a large number of clinical research data. Johns Hopkins University School of Medicine reported the effect of paclitaxel on advanced ovarian cancer.
The curative effect is amazing and has been included in the domestic medical yearbook 1989. In the same year, Squibb was appointed by the National Cancer Institute.
As a partner, * * * will jointly develop and industrialize paclitaxel. 199 1 year, director of the national cancer institute.
Dr. Broder asserted that paclitaxel will become the most important anticancer drug in the world in the next 15 years. 1992 65438+ February, paclitaxel
Approved by the US Food and Drug Administration, it has become a therapeutic drug for advanced ovarian cancer. Then approve the use.
Can be used for treating breast cancer. Today, paclitaxel has been widely used to treat breast cancer, lung cancer, ovarian cancer and cancer.
Treat various malignant tumors, including spirochete sarcoma. In addition, the efficacy of paclitaxel on other tumors is being further studied.
Experiments have proved that it also has potential curative effect on many other tumors. The US National Food and Drug Administration has also obtained
A large number of data about the clinical efficacy and adverse reactions of paclitaxel were presented.
Paclitaxel is the best drug to treat ovarian cancer and breast cancer, and its price is very expensive. The market price is 4800 yuan.
Dollar/gram. And its natural resources-yew and East African Podocarpus (1999)-are all growing places.
It is slow, limited in quantity and low in effective components. At first, all paclitaxel used for treatment came from Thailand.
It takes a 600-year-old yew tree to treat a patient. Now paclitaxel and its anticancer homologous derivatives
Compounds can be prepared by chemical semisynthesis of their precursors. These precursors include 10- deacetylbacardine III and bacardine III.
, 10- deacetyl paclitaxel, 10- deacetyl cephalomannine, 7- valeraldehyde-10- deacetyl paclitaxel, etc. Before all this
They can all be separated from Taxus chinensis. At the same time, another semi-synthetic chemical product violet has a better therapeutic effect on ovarian cancer.
Flavane prepared by Rhone-Poulenc Rorer Company has also been approved by the State Food and Drug Administration as a drug for the treatment of intractable diseases.
Therapeutic drugs for malignant ovarian cancer. These studies have alleviated the shortage of drug sources to some extent, but they must be solved.
We still have a long way to go.
A brief history of paclitaxel
1958 The American National Cancer Institute extracts anticancer substances from plants all over the world.
Taxol was found in Taxus chinensis 197 1 year, and its anticancer mechanism is unique.
1992, the American government transferred the patent to Squibb, and paclitaxel came out.
1994 paclitaxel became the global sales champion of anticancer drugs.
In 2000, the sales of paclitaxel reached10 billion (the supply of raw materials did not increase further).
In 2002, the central government issued a document prohibiting the felling of wild yew and encouraging artificial planting.
Squibb's patent expired in 2004, and more pharmaceutical companies around the world intervened in the production of paclitaxel.
In 2004, Huayuan began to operate the Taxus project and set up a taxol refining and processing plant directly under it, with the goal of China and even Asia.
The largest yew base.
In 2005, the central government issued a document again to carry out a nationwide survey of Taxus resources and encourage planting.
In 2005, the project was invested by individual investors.