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Maytansine

Maytansine
Maytansine

Chemical Name: L-alanine, N-acetyl-N-methyl-, 11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03, 5]hexacosa-10,12,14(26),16,18-pentaen-6-yl ester, [1S-(1R*,2S*,3R*,5R*,6R*,16E,18E,20S*,21R*)]

Molecular Weight: 692.19614
Formula: C34H46ClN3O10
CAS#: 35846-53-8

Biological Activity
Maytansine, a benzoansamacrolide, is a highly potent microtubule-targeted compound that induces mitotic arrest and kills tumor cells at subnanomolar concentrations. However, it failed as an anticancer agent in human clinical trials because of lack of tumor specificity and unacceptable systemic toxicity. The potent cell killing ability of maytansine can be used in a targeted delivery approach, such as an antibody-drug conjugate, for the selective delivery of the drug and destruction of cancer cells. [1-6]

The ansamycin antibiotic was originally isolated from the Ethiopian shrub Maytenus serrata and binds to tubulin at the rhizoxin binding site. It inhibits microtubule assembly, induces microtubule disassembly, and disrupts mitosis. Maytansine exhibits cytotoxicity against many tumor cell lines and may inhibit tumor growth in vivo. [5 – 15]

Maytansine and its analogs (maytansinoids DM1 and DM4) are potent microtubule-targeted compounds that inhibit proliferation of cells at mitosis. The antibody-maytansinoid conjugates consist of maytansinoids attached to tumor-specific antibodies.

See: ADC Review / Knowledge Center 


References:
[1] Lopus M, Oroudjev E, Wilson L, Wilhelm S, Widdison W, Chari R, Jordan MA. Maytansine and cellular metabolites of antibody-maytansinoid conjugates strongly suppress microtubule dynamics by binding to microtubules. Mol Cancer Ther. 2010 Oct;9(10):2689-99.<br>
[2] Widdison WC, Wilhelm SD, Cavanagh EE, Whiteman KR, Leece BA, Kovtun Y, Goldmacher VS, Xie H, Steeves RM, Lutz RJ, Zhao R, Wang L, Blättler WA, Chari RV. Semisynthetic maytansine analogues for the targeted treatment of cancer. J Med Chem. 2006 Jul 13;49(14):4392-408.<br>
[3] Liu Z, Floss HG, Cassady JM, Chan KK. Metabolism studies of the anti-tumor agent maytansine and its analog ansamitocin P-3 using liquid chromatography/tandem mass spectrometry. J Mass Spectrom. 2005 Mar;40(3):389-99.<br>
[4] Tassone P, Gozzini A, Goldmacher V, Shammas MA, Whiteman KR, Carrasco DR, Li C, Allam CK, Venuta S, Anderson KC, Munshi NC. In vitro and in vivo activity of the maytansinoid immunoconjugate huN901-N2′-deacetyl-N2′-(3-mercapto-1-oxopropyl)-maytansine against CD56+ multiple myeloma cells. Cancer Res. 2004 Jul 1;64(13):4629-36.<br>
[5] Iwasaki S. [Inhibitors of tubulin assembly: specially on rhizoxin-maytansine site ligands]. Tanpakushitsu Kakusan Koso. 1993 Aug;38(11):1742-52. Review in Japanese.<br>
[6] Sawada T, Kato Y, Kobayashi H, Hashimoto Y, Watanabe T, Sugiyama Y, Iwasaki S. A fluorescent probe and a photoaffinity labeling reagent to study the binding site of maytansine and rhizoxin on tubulin. Bioconjug Chem. 1993 Jul-Aug;4(4):284-9.<br>
[7] Hamel E. Natural products which interact with tubulin in the vinca domain: maytansine, rhizoxin, phomopsin A, dolastatins 10 and 15 and halichondrin B. Pharmacol Ther. 1992;55(1):31-51. Review.<br>
[8] Takahashi M, Iwasaki S, Kobayashi H, Okuda S, Murai T, Sato Y. Rhizoxin binding to tubulin at the maytansine-binding site. Biochim Biophys Acta. 1987 Dec 7;926(3):215-23.<br>
[9] Suchocki JA, Sneden AT. Characterization of decomposition products of maytansine. J Pharm Sci. 1987 Sep;76(9):738-43.<br>
[10] Luduena RF, Anderson WH, Prasad V, Jordan MA, Ferrigni KC, Roach MC, Horowitz PM, Murphy DB, Fellous A. Interactions of vinblastine and maytansine with tubulin. Ann N Y Acad Sci. 1986;466:718-32.<br>
[11] Fellous A, Ludueña RF, Prasad V, Jordan MA, Anderson W, Ohayon R, Smith PT. Effects of Tau and MAP2 on the interaction of maytansine with tubulin: inhibitory effect of maytansine on vinblastine-induced aggregation of tubulin. Cancer Res. 1985 Oct;45(10):5004-10.<br>
[12] Schibler MJ, Cabral FR. Maytansine-resistant mutants of Chinese hamster ovary cells with an alteration in alpha-tubulin. Can J Biochem Cell Biol. 1985 Jun;63(6):503-10.<br>
[13] Huang AB, Lin CM, Hamel E. Maytansine inhibits nucleotide binding at the exchangeable site of tubulin. Biochem Biophys Res Commun. 1985 May 16;128(3):1239-46.<br>
[14] Ravry MJ, Omura GA, Birch R. Phase II evaluation of maytansine (NSC 153858) in advanced cancer. A Southeastern Cancer Study Group trial. Am J Clin Oncol. 1985 Apr;8(2):148-50.<br>
[15] Phase II trials of maytansine, low-dose chlorozotocin, and high-dose chlorozotocin as single agents against advanced measurable adenocarcinoma of the pancreas. Gastrointestinal Tumor Study Group. Cancer Treat Rep. 1985 Apr;69(4):417-20.


Last Editorial Review: March 16, 2015

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