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| Names | |
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| IUPAC name
N-Acetyl-N-methyl-L-alanine(1S-(1R*,2S*,3R*,5R*,6R*,16E,18E,20S*,21R*))-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethy-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo(19.3.1.1(sup 10,14).0(sup 3,5))hexacosa-10,12,14(26),16,18-pentaen-6-yl ester
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| Other names
Maytansin
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| Identifiers | |
3D model (JSmol)
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| ChEBI | |
| ChEMBL | |
| ChemSpider | |
PubChem CID
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| UNII | |
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| Properties | |
| C34H46ClN3O10 | |
| Molar mass | 692.20 g/mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Maitansine (INN), or maytansine (USAN), is a cytotoxic agent. It inhibits the assembly of microtubules by binding to tubulin at the rhizoxin binding site,[1] with a KD of approximately 1 μmol/L.[2] This property made Maitansine a potential anti-cancer drug, with an IC50 of 1.6 x 10-11 M in vivo, approximately 100 to 1000 times more toxic than other anti-cancer drugs.[3] This high toxicity and its lack of specificity resulted in unsuccessful clinical trials.[2]
It is an antibiotic macrolide of the ansamycin type and can be isolated from plants of the genus Maytenus.[1] It is believed to first have been isolated from either Maytenus serrata or Maytenus ovatus.[4][2]
Maytansinoids
edit
Derivatives of maitansine are known as maytansinoids formed by changing the R-group[5], shown in red in the above image, to increase target specificity.[2][6] Target specificity is improved by conjugating the maitansinoids to antibodies.[2]
These derivatives also do not inhibit microtubule assembly as well as Maytansine, but have been seen to suppress dynamic instability, the stochastic switches between growing and shortening, more strongly.[2] Some are being investigated as the cytotoxic component of antibody-drug conjugates for cancer treatment,[3] and the antibody-drug conjugate trastuzumab emtansine is an approved drug for the treatment of certain kinds of breast cancer in the EU and in the US.[6][7]
Examples of maytansinoids are:
- Ansamitocin[5]
- Mertansine / emtansine (DM1)
- Ravtansine / soravtansine (DM4)
See also
edit- ImmunoGen, developer of maytansinoid based drugs
References
edit- ^ a b National Cancer Institute: Definition of Maytansine
- ^ a b c d e f Lopus, M; Oroudjev, E; Wilson, L; Wilhelm, S; Widdison, W; Chari, R; Jordan, MA (2010). "Maytansine and cellular metabolites of antibody-maytansinoid conjugates strongly suppress microtubule dynamics by binding to microtubules". Mol Cancer Ther. 9 (10): 2689–99. doi:10.1158/1535-7163.MCT-10-0644. PMC 2954514. PMID 20937594.
- ^ a b Chari, RV; Martell, BA; Gross, JL; et al. (January 1992). "Immunoconjugates containing novel maytansinoids: promising anticancer drugs" (PDF). Cancer Res. 52 (1): 127–31. PMID 1727373.
- ^ "NCI Thesaurus". ncithesaurus.nci.nih.gov. Retrieved 2023-04-27.
- ^ a b Yu, T.-W.; Bai, L; Clade, D; Hoffmann, D; Toelzer, S; Trinh, KQ; Xu, J; Moss, SJ; Leistner, E (2002). "The biosynthetic gene cluster of the maytansinoid antitumor agent ansamitocin from Actinosynnemapretiosum". Proceedings of the National Academy of Sciences. 99 (12): 7968–7973. Bibcode:2002PNAS...99.7968Y. doi:10.1073/pnas.092697199. PMC 123004. PMID 12060743.
- ^ a b "Kadcyla EPAR". European Medicines Agency (EMA). 17 September 2018.
- ^ "Drug Approval Package: ado-trastuzumab emtansine". U.S. Food and Drug Administration (FDA). 22 February 2013. Archived from the original on 4 December 2019. Retrieved 3 December 2019.