Paclitaxel 

T7402, Paclitaxel

Potent anti-neoplastic drug; binds to the N-terminal region of β-tubulin and promotes the formation of highly stable microtubules that resist depolymerization, thus preventing normal cell division and arresting the cell cycle at the G₂/M phase. The microtubule damage induces apoptosis through a JNK-dependent pathway in the early phase followed by a JNK-independent pathway, perhaps related to the activation of protein kinase A or of Raf-1 kinase, that results in phosphorylation of Bcl-2. Major metabolite in human liver microsome is 6α-hydroxypaclitaxel (6α-OHP). This enzymatic conversion can be used as a potential marker reaction for human CYP2C8.

1, 25 mg in glass btl

Taxol® is a registered trademark of Bristol-Myers Squibb

Taxol is a registered trademark of Bristol-Myers Squibb Co.

95%

[α]20/D −49°, c = 1 in methanol

≤1% methyl alcohol and ethyl alcohol

213 °C (dec.)(lit.)

human ... BCL2(596)

Parekh, H., and Simpkins, H., The transport and binding of taxol. Gen. Pharmacol. 29, 167-172, (1997)

Shtil, A.A., et al., Differential regulation of mitogen-activated protein kinases by microtubule-binding agents in human breast cancer cells. Oncogene 18, 377-384, (1999)

Wang, T.H., et al., Microtubule dysfunction induced by paclitaxel initiates apoptosis through both c-Jun N-terminal kinase (JNK)‑dependent and -independent pathways in ovarian cancer cells. J. Biol. Chem. 274, 8208, (1999)

Jordan, A., et al., Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med. Res. Rev. 18, 259-296, (1998)

Srivastava, R.K., et al., Involvement of microtubules in the regulation of Bcl2 phosphorylation and apoptosis through cyclic AMP-dependent protein kinase. Mol. Cell. Biol. 18, 3509-3517, (1998)

Lutz, E.S., et al., Monolithic silica rod liquid chromatography with ultraviolet or fluorescence detection for metabolite analysis of cytochrome P450 marker reactions. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 780, 205-215, (2002)

Torres, K., and Horwitz, S.B., Mechanisms of Taxol-induced cell death are concentration dependent. Cancer Res. 58, 3620-3626, (1998)

Merck 13,7052

Beil. 18,V,622

1

DA8340700