Mertansine

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Mertansine
Mertansine skeletal.svg
Names
Other names
Maytansinoid DM1
N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
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).
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Infobox references

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).

ADCs with this design include trastuzumab emtansine, lorvotuzumab mertansine, and cantuzumab mertansine. Some are still experimental; others are in regular clinical use.

Mechanism of action[edit]

Mertansine is a tubulin inhibitor, meaning that it inhibits the assembly of microtubules by binding to tubulin (at the rhizoxin binding site).[1]

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.

Uses and chemistry[edit]

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.[2]

ADCs include:

Mertansine linked to a monoclonal antibody (mab). The part where mertansine differs from its parent compound maytansine is shown red. The linker 4-mercaptovaleric acid is shown blue.

Emtansine[edit]

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[5] as well as by the World Health Organization (WHO)[6] despite the fact that the linker contains only one imide group according to the WHO.[2]

DM1 and its attachment via these linkers result from ImmunoGen Inc research.

An example is:

Emtansine mab structure coloured.svg

References[edit]