Mertansine, also called DM1 (and in some of its forms emtansine), is a thiol-containing maytansinoid that for therapeutic purposes is attached to a monoclonal antibody through reaction of the thiol group with a linker structure to create an antibody-drug conjugate (ADC).[1]
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Names | |
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Other names Maytansinoid DM1 N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine | |
Identifiers | |
3D model (JSmol) | |
ChEBI | |
ChemSpider | |
ECHA InfoCard | 100.168.831 |
PubChem CID | |
UNII | |
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Properties | |
C35H48ClN3O10S | |
Molar mass | 738.29 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
ADCs with this design include trastuzumab emtansine, lorvotuzumab mertansine, and cantuzumab mertansine. Some are still experimental; others are in regular clinical use.[citation needed]
Mechanism of action
Mertansine is a tubulin inhibitor, meaning that it inhibits the assembly of microtubules by binding to tubulin (at the rhizoxin binding site).[2]
The monoclonal antibody binds specifically to a structure (usually a protein) occurring in a tumour, thus directing mertansine into this tumour. This concept is called targeted therapy.[citation needed]
Uses and chemistry
The following (experimental) drugs are antibody-drug conjugates (ADC) combining monoclonal antibodies with mertansine as the cytotoxic component. Mertansine is linked via 4-mercaptovaleric acid.[3]
ADCs include:
- Bivatuzumab mertansine
- Cantuzumab mertansine[4]
- Lorvotuzumab mertansine (IMGN901) for CD56 positive cancers, for example multiple myeloma[5]
![](http://upload.wikimedia.org/wikipedia/commons/thumb/c/c8/Mertansine_mab_structure_coloured.svg/522px-Mertansine_mab_structure_coloured.svg.png)
Emtansine
DM1 can also be linked via a more complicated structure – 4-(3-mercapto-2,5-dioxo-1-pyrrolidinylmethyl)-cylohexanecarboxylic acid or SMCC –, in which case the International Nonproprietary Name of the conjugate formed contains the word emtansine. The abbreviation comes from the chemical designation "succinimidyl-trans-4-(maleimidylmethyl) cyclohexane-1-carboxylate" which is used in the primary literature[6] as well as by the World Health Organization (WHO)[7] despite the fact that the linker contains only one imide group according to the WHO.[3]
DM1 and its attachment via these linkers result from ImmunoGen Inc research.
An example is:
- Trastuzumab emtansine (T-DM1), an anti-HER2/neu antibody-drug conjugate[8][9]
![](http://upload.wikimedia.org/wikipedia/commons/thumb/7/7b/Emtansine_mab_structure_coloured.svg/590px-Emtansine_mab_structure_coloured.svg.png)