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Baccatin III (left) Paclitaxel (right)

10-Deacetylbaccatin (left) Docetaxel (right)

Taxanes are a class of diterpenes. They were originally identified from plants of the genus Taxus (yews), and feature a taxadiene core. Paclitaxel (Taxol) and docetaxel (Taxotere) are widely used as chemotherapy agents.^[1]^[2] Cabazitaxel was FDA approved to treat hormone-refractory prostate cancer.

Taxanes present difficulties in formulation 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 synthesized artificially. Paclitaxel was originally derived from the Pacific yew tree. Taxanes are difficult to synthesize because of their numerous chiral centres — taxol has 11 of these.

Recently, the presence of taxanes in the shells and leaves of Corylus avellana (the common hazel plant) has been reported.^[3]^[4]

Mechanism of action

The principal mechanism of action of the taxane class of drugs is the disruption of microtubule function. Microtubules are essential to cell division, and taxanes stabilize GDP-bound tubulin in the microtubule, thereby inhibiting the process of cell division as depolymerization is prevented. Thus, in essence, taxanes are mitotic inhibitors. In contrast to the taxanes, the vinca alkaloids prevent mitotic spindle formation through inhibition of tubulin polymerization. Both taxanes and vinca alkaloids are, therefore, named spindle poisons or mitosis poisons, but they act in different ways. Taxanes are also thought to be radiosensitizing.

Substances

Hongdoushans A-C are oxygenated taxane diterpenes, isolated from the wood of Taxus wallichiana. Hongdoushan A (C₂₉H₄₄O₇), hongdoushan B (C₂₇H₄₀O₇), and hongdoushan C (C₂₇H₄₂O₆) are reported to have anticancer activity in vitro.^[5]

Names

Taxanes are usually treated as synonymous with taxoids. The name "taxol" began as a common noun (analogous with other terms in which a genus name root was suffixed with -ol or -in), but it was later capitalized as a trade name, and the international nonproprietary name of the compound is paclitaxel.

References

^ Hagiwara, H.; Sunada, Y. (2004). "Mechanism of taxane neurotoxicity". Breast cancer (Tokyo, Japan). 11 (1): 82–85. PMID 14718798.
^ Rowinsky, MD, Eric K. (February 1997). "THE DEVELOPMENT AND CLINICAL UTILITY OF THE TAXANE CLASS OF ANTIMICROTUBULE CHEMOTHERAPY AGENTS". Annual Review of Medicine. 48 (1): 353–374. doi:10.1146/annurev.med.48.1.353.
^ Ottaggio, Laura; Bestoso, Federica; Armirotti, Andrea; Balbi, Alessandro; Damonte, Gianluca; Mazzei, Mauro; Sancandi, Monica; Miele, Mariangela (2008). "Taxanes from Shells and Leaves of Corylus avellana". Journal of Natural Products. 71 (1): 58–60. doi:10.1021/np0704046. PMID 18163585. Retrieved 2016-12-11.
^ Hoffman, Angela M; Shahidi, Fereidoon (January 2009). "Paclitaxel and other taxanes in hazel". Journal of Functional Foods. 1 (1): 33–37. doi:10.1016/j.jff.2008.09.004. Retrieved 2016-12-11.
^ Banskota AH, Usia T, Tezuka Y, Kouda K, Nguyen NT, Kadota S (2002). "Three new C-14 oxygenated taxanes from the wood of Taxus yunnanensis.". J Nat Prod. 65 (11): 1700–2. doi:10.1021/np020235j. PMID 12444707.

External links

Media related to taxanes at Wikimedia Commons

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1. 非プラチナ製剤ベースの癌化学療法の神経学的合併症の概要 overview of neurologic complications of non platinum cancer chemotherapy
2. タキサン誘発性肺毒性 taxane induced pulmonary toxicity
3. 乳癌に対する術前補助化学療法：理論的根拠、治療前評価、および治療法の選択肢 neoadjuvant therapy for breast cancer rationale pretreatment evaluation and therapeutic options
4. 成人における抗癌剤の投与 dosing of anticancer agents in adults
5. 全身化学療法に対する輸注反応 infusion reactions to systemic chemotherapy

English Journal

Infrared and Raman spectroscopic methods for characterization of Taxus baccata L. - Improved taxane isolation by accelerated quality control and process surveillance.

Gudi G1, Krähmer A2, Koudous I3, Strube J4, Schulz H5.
Talanta.Talanta.2015 Oct 1;143:42-9. doi: 10.1016/j.talanta.2015.04.090. Epub 2015 May 8.
Different yew species contain poisonous taxane alkaloids which serve as resources for semi-synthesis of anticancer drugs. The highly variable amounts of taxanes demand new methods for fast characterization of the raw plant material and the isolation of the target structures during phyto extraction.
PMID 26078126

A novel anti-microtubule agent with carbazole and benzohydrazide structures suppresses tumor cell growth in vivo.

Ohira M1, Iwasaki Y1, Tanaka C1, Kuroki M1, Matsuo N1, Kitamura T1, Yukuhiro M1, Morimoto H2, Pang N2, Liu B2, Kiyono T3, Amemiya M4, Tanaka K5, Yoshida K1, Sugimoto N1, Ohshima T6, Fujita M7.
Biochimica et biophysica acta.Biochim Biophys Acta.2015 Sep;1850(9):1676-84. doi: 10.1016/j.bbagen.2015.04.013. Epub 2015 May 7.
BACKGROUND: The mitotic spindles are among the most successful targets of anti-cancer chemotherapy, and they still hold promise as targets for novel drugs. The anti-mitotic drugs in current clinical use, including taxanes, epothilones, vinca alkaloids, and halichondrins, are all microtubule-targetin
PMID 25960391

Impact of tumor angiogenic profile on the outcome of patients with metastatic breast carcinoma treated with weekly docetaxel. A Hellenic Cooperative Oncology Group (HeCOG) study.

Kourea HP1, Kotoula V2, Koutras A3, Alexopoulou Z4, Papaspirou I5, Skarlos DV6, Efstratiou I7, Bobos M8, Zagouri F9, Papakostas P10, Pectasides D11, Chrisafi S8, Varthalitis I12, Aravantinos G13, Kosmidis P14, Bafaloukos D15, Scopa CD16, Fountzilas G17.
Histology and histopathology.Histol Histopathol.2015 Sep;30(9):1129-41. doi: 10.14670/HH-11-612. Epub 2015 Mar 25.
BACKGROUND: Metronomic taxane administration has putative antiangiogenic properties. Herein, we examined the baseline tumor angiogenic profile of patients with metastatic breast carcinoma (MBC) in a prospective-retrospective translational research study. The interplay between the angiogenic factors
PMID 25807307

Japanese Journal

^<18>F-Fluorodeoxyglucose positron emission tomography optimizes neoadjuvant chemotherapy for primary breast cancer to achieve pathological complete response

UEDA Shigeto,SAEKI Toshiaki,SHIGEKAWA Takashi,OMATA Jiro,MORIYA Tomoyuki,YAMAMOTO Junji,OSAKI Akihiko,FUJIUCHI Nobuko,MISUMI Misono,TAKEUCHI Hideki,SAKURAI Takaki,TSUDA Hitoshi,TAMURA Katsumi,ISHIDA Jiro,ABE Yoshiyuki,IMABAYASHI Etsuko,KUJI Ichiei,MATSUDA Hiroshi
International journal of clinical oncology 17(3), 276-282, 2012-06-01
NAID 10030951681

A rapid and sensitive LC/ESI-MS/MS method for quantitative analysis of docetaxel in human plasma and its application to a pharmacokinetic study.

Yamaguchi Hiroaki,Fujikawa Asuka,Ito Hajime,Tanaka Nobuaki,Furugen Ayako,Miyamori Kazuaki,Takahashi Natsuko,Ogura Jiro,Kobayashi Masaki,Yamada Takehiro,Mano Nariyasu,Iseki Ken
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 893-894, 157-161, 2012-04-15
… Docetaxel is a taxane family antineoplastic agent widely employed in cancer chemotherapy. …
NAID 120004856992

Relationship between the Structures of Taxane Derivatives and Their Microtubule Polymerization Activity

HIDAKA Masafumi,KOGA Tomoe,KIYOTA Hiromasa,HORIGUCHI Tohru,SHI Qing-Wen,HIROSE Keiko,UCHIDA Takafumi
Bioscience, biotechnology, and biochemistry 76(2), 349-352, 2012-02-23
… The structure of paclitaxel is composed of two key elements, a taxane ring and an <I>N</I>-benzoylphenylisoserine side chain at C-13. … A number of natural and artificial compounds with taxane skeletons have been isolated, but almost none of their bioactivities have been evaluated. … In this study, we focused on compounds having a taxane skeleton structure and examined their effects on tubulin dynamics. …
NAID 10030400057