Mertansine

Mertansine

Names
Other names Maytansinoid DM1 N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine
Identifiers
ChEBI	CHEBI:82755 N
Jmol interactive 3D	Image
PubChem	11343137
InChI InChI=1S/C35H48ClN3O10S/c1-19-10-9-11-26(46-8)35(44)18-25(47-33(43)37-35)20(2)31-34(4,49-31)27(48-32(42)21(3)38(5)28(40)12-13-50)17-29(41)39(6)23-15-22(14-19)16-24(45-7)30(23)36/h9-11,15-16,20-21,25-27,31,44,50H,12-14,17-18H2,1-8H3,(H,37,43)/b11-9+,19-10+/t20-,21+,25+,26-,27+,31+,34+,35+/m1/s1 N Key: ANZJBCHSOXCCRQ-FKUXLPTCSA-N N
SMILES CC1C2CC(C(C=CC=C(CC3=CC(=C(C(=C3)OC)Cl)N(C(=O)CC(C4(C1O4)C)OC(=O)C(C)N(C)C(=O)CCS)C)C)OC)(NC(=O)O2)O
Properties
Chemical formula	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).
N verify (what is YN ?)
Infobox references

Mertansine refers to the thiol-containing maytansinoid DM1, which 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).

Experimental ADCs with this design include lorvotuzumab mertansine.

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).^[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

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:

• Bivatuzumab mertansine
• Cantuzumab mertansine^[3]
• Lorvotuzumab mertansine (IMGN901) for CD56 positive cancers, for example multiple myeloma^[4]

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^[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:

• Trastuzumab emtansine (T-DM1), an anti-HER2/neu antibody-drug conjugate^[7][8]

References