Taxanes are a class of

diterpene Diterpenes are a class of chemical compounds composed of four isoprene units, often with the molecular formula C20H32. They are biosynthesized by plants, animals and fungi via the HMG-CoA reductase pathway, with geranylgeranyl pyrophosphate being ...

s. They were originally identified from plants of the genus ''

Taxus ''Taxus'' is a genus of coniferous trees or shrubs known as yews in the family Taxaceae. They are relatively slow-growing and can be very long-lived, and reach heights of , with trunk girth averaging . They have reddish bark, lanceolate, flat, ...

'' (yews), and feature a

taxadiene Taxadiene (taxa-4,11-diene) is a diterpene. Taxadiene is the first committed intermediate in the synthesis of taxol. Six hydroxylation reactions, and a few others, are needed to convert taxadiene to baccatin III. Enzymatically, taxadiene is prod ...

core.

Paclitaxel Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer ...

(Taxol) and

docetaxel Docetaxel (DTX or DXL), sold under the brand name Taxotere among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer, head and neck cancer, stomach cancer, prostate cancer and non-small-ce ...

(Taxotere) are widely used as

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

agents.

Cabazitaxel Cabazitaxel, sold under the brand name Jevtana, is a semi-synthetic derivative of a natural taxoid. It is a microtubule inhibitor, and the fourth taxane to be approved as a cancer therapy. Cabazitaxel was developed by Sanofi-Aventis and was ap ...

was FDA approved to treat hormone-refractory

prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...

. Taxanes present difficulties in

formulation Formulation is a term used in various senses in various applications, both the material and the abstract or formal. Its fundamental meaning is the putting together of components in appropriate relationships or structures, according to a formul ...

as medicines because they are poorly soluble in water.

Production

As their name suggests, taxanes were first derived from natural sources, but some have been semisynthesized. Paclitaxel was originally derived from the

Pacific yew ''Taxus brevifolia'', the Pacific yew or western yew, is a species of tree in the yew family Taxaceae native to the Pacific Northwest of North America. It is a small evergreen conifer, thriving in moisture and otherwise tending to take the form o ...

tree. Taxanes are difficult to synthesize because of their numerous

chiral Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is distinguishable from ...

centres—taxol has 11 of these. Recently, the presence of taxanes in the shells and leaves of ''

Corylus avellana ''Corylus avellana'', the common hazel, is a species of flowering plant in the birch family Betulaceae. It is native to Europe and western Asia. It is an important component of the hedgerows that were the traditional field boundaries in lowland En ...

'' (the common hazel plant) has been reported.

Mechanism of action

The principal mechanism of action of the taxane class of drugs is the disruption of

microtubule Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...

function. Microtubules are essential to cell division, and taxanes stabilize

GDP Gross domestic product (GDP) is a monetary measure of the market value of all the final goods and services produced and sold (not resold) in a specific time period by countries. Due to its complex and subjective nature this measure is ofte ...

-bound

tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoske ...

in the microtubule, thereby inhibiting the process of cell division as ''depolymerization'' is prevented. Thus, in essence, taxanes are

mitotic inhibitor A mitotic inhibitor is a drug that inhibits mitosis, or cell division. These drugs disrupt microtubules, which are structures that pull the chromosomes apart when a cell divides. Mitotic inhibitors are used in cancer treatment, because cancer cell ...

s. In contrast to the taxanes, the

vinca alkaloids ''Vinca'' alkaloids are a set of anti-mitotic and anti-microtubule alkaloid agents originally derived from the periwinkle plant ''Catharanthus roseus'' (basionym ''Vinca rosea'') and other ''vinca'' plants. They block beta-tubulin polymerizatio ...

prevent

mitotic spindle In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a pr ...

formation through inhibition of

''polymerization''. Both taxanes and vinca alkaloids are, therefore, named

spindle poison A spindle poison, also known as a spindle toxin, is a poison that disrupts cell division by affecting the protein threads that connect the centromere regions of chromosomes, known as spindles. Spindle poisons effectively cease the production of new ...

s or mitosis poisons, but they act in different ways. Taxanes are also thought to be

radiosensitizing A radiosensitizer is an agent that makes tumor cells more sensitive to radiation therapy. It is sometimes also known as a radiation sensitizer or radio-enhancer. Mechanism of action Conventional chemotherapeutics are currently being used in con ...

Substances

Hongdoushans A–C are oxygenated taxane diterpenes, isolated from the wood of ''

Taxus wallichiana ''Taxus wallichiana'', the Himalayan yew, is a species of yew, native to the Himalaya and parts of south-east Asia. The species has a variety of uses in traditional medicine. It is currently classified as endangered by the IUCN. Distribution a ...

''. Hongdoushan A (C₂₉H₄₄O₇), hongdoushan B (C₂₇H₄₀O₇), and hongdoushan C (C₂₇H₄₂O₆) are reported to have anticancer activity ''in vitro''. Taxuspines A–D have been isolated from ''Taxus''.

Names

Taxanes are usually treated as

synonym A synonym is a word, morpheme, or phrase that means exactly or nearly the same as another word, morpheme, or phrase in a given language. For example, in the English language, the words ''begin'', ''start'', ''commence'', and ''initiate'' are all ...

ous with

taxoid Taxoids are a class of derivatives from taxol, that is, paclitaxel. They were developed for their anticancer chemotherapeutic properties. Taxoids are usually treated as synonymous with taxanes; for example, a major medical dictionary defines the ...

s. The name "taxol" began as a common noun (analogous with other terms in which a genus name root was

suffix In linguistics, a suffix is an affix which is placed after the stem of a word. Common examples are case endings, which indicate the grammatical case of nouns, adjectives, and verb endings, which form the conjugation of verbs. Suffixes can carry ...

ed with '' -ol'' or '' -in''), but it was later capitalized as a trade name, and the international nonproprietary name of the compound is paclitaxel.

References

External links