Paclitaxel Taxol

Mitotic inhibitors (antimitotics) interfere with or stop cell division. Examples of mitotic inhibitors include paclitaxel (Taxol) and vincristine (Oncovin). 

Sparreboom A, van Asperen J, Mayer U, Schinkel AH, Smit JW, Meijer DK, et al. Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc Natl Acad Sci USA 1997 94 2031-5. 

Certain drugs bind to microtubules and thus interfere with their assembly or disassembly. These include colchicine (used for treatment of acute gouty arthritis), vinblastine (a vinca alkaloid used for treating certain types of cancer), paclitaxel (Taxol) (effective against ovarian cancer), and griseoflilvin (an antifungal agent). 

Figure 4.48 Synthesis map showing starting materials used for the synthesis of paclitaxel (taxol).

Table 4.21 Summary of reaction metrics and synthesis tree parameters for paclitaxel (taxol) synthesis plans ranked according to overall kernel (maximum) RME. ...

Kanazawa, A.M., Denis, J.N., Greene, A.E. (1994) Direct, Stereoselective Synthesis ofthe Protected Paclitaxel (Taxol) Side Chain and High-Yield Transformation to Paclitaxel. Chemical Communications, 2591-2592. 

The significance of P-gp, however, in affecting absorption and bioavailability of P-gp substrate drugs can be seen in studies in knockout mice that do not have intestinal P-gp. The gene responsible for producing that protein has been knocked out of the genetic repertoire. Those animals evidenced a sixfold increase in plasma concentrations (and AUC, area under the plasma concentration-time curve) of the anticancer drug paclitaxel (Taxol) compared to the control animals [54]. Another line of evidence is the recent report... 

V-bromo-benzamide is a useful method for the synthesis of the side chain of paclitaxel (taxol) from isopropyl cinnamate.219... 

Structure 1 vinblastine, 2 vincristine, 3 maytansine, 4 rhizoxin and 5 paclitaxel (Taxol)... 

A fine example of such a semi-synthesis is the preparation of the anti-cancer drug paclitaxel (Taxol ), a relatively scarce compound from Taxus brevifolia. Here, the natural and better accessible 10-deacetylbaccatin III, isolated from the leaves of Taxus baccata, provides the complicated ring system of paclitaxel, including all substituents with the right stereostructure (Scheme 5.1). In just four reaction steps [5] paclitaxel is obtained from 10-deacetylbaccatin III. 

Yen WC, Corpuz MR, Prudente RY, Cooke TA, Bissonnette RP, Negro-Vilar A, Lamph WW (2004) A selective retinoid X receptor agonist bexarotene (Targretin) prevents and overcomes acquired paclitaxel (Taxol) resistance in human non-small cell lung cancer. Clin Cancer Res 10(24) 8656-8664. 

S. W. Mamber, A. B. Mikkilineni, E. J. Pack, M. P. Rosser, H. Wong, Y. Ueda, S. Fo-renza, Tubulin Polymerization by Paclitaxel (Taxol) Phosphate Prodrugs after Metabolic Activation by Alkaline Phosphatase , J. Pharmacol. Exp. Then 1995, 274, 877-883. 

Paclitaxel (Taxol, Bristol-Myers Squibb) is a chemotherapy drug for ovarian cancer, breast cancer, and certain lung cancers. It was discovered by the US National Cancer Institute in the 1960s. Originally, it was extracted from the bark of the North American yew tree (Taxus brevifo-lia). Clinical tests had necessitated the harvesting of the bark, and this method damaged the trees irreversibly. 

Jordan MA, Wendell K, GardinerS, Derry WB, CoppH, Wilson L. Mitotic block induced in HeLa cells by low concentrations of paclitaxel (Taxol) results in abnormal mitotic exit and apoptotic cell death. Cancer Res 1996 56(4) 816-825. 

Hennequin C, Giocanti N, Favaudon V. Interaction of ionizing radiation with paclitaxel (Taxol) and docetaxel (Taxotere) in HeLa and SQ20B cells. Cancer Res 1996 56(8) 1842-1850. 

Mason KA, Milas L, Peters LJ. Effect of paclitaxel (taxol) alone and in combination with radiation on the gastrointestinal mucosa. Int J Radiat Oncol Biol Phys 1995 32(5) 1381-1389. 

Vermorken J, Catimel G, Mulder PD, et al. Randomized phase II trial of weekly methotrexate (MTX) versus two schedules of triweekly paclitaxel (taxol) in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). ProcAnnu Meet Am Soc Clin Oncol 1999 18 A 1527. 

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