Mertansine, also called DM1 (and in some of its forms emtansine), is a

thiol In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl gro ...

-containing maytansinoid that for therapeutic purposes is attached to a

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ...

through reaction of the thiol group with a linker structure to create an

antibody-drug conjugate Antibody-drug conjugates or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. Unlike chemotherapy, ADCs are intended to target and kill tumor cells while sparing healthy cells. As of 2019, some 56 phar ...

(ADC). ADCs with this design include

trastuzumab emtansine Trastuzumab emtansine, sold under the brand name Kadcyla, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the cytotoxic agent DM1. Trastuzumab alone stops growth of can ...

, lorvotuzumab mertansine, and

cantuzumab mertansine Cantuzumab mertansine (SB-408075; huC242-DM1) is an antibody-drug conjugate investigated to treat colorectal cancer and other types of cancer. It is a humanized monoclonal antibody, cantuzumab (huC242) linked to a cytotoxic agent, mertansine (DM1 ...

. Some are still experimental; others are in regular clinical use.

Mechanism of action

Mertansine is a tubulin inhibitor, meaning that it inhibits the assembly of microtubules by binding to

tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytosk ...

(at the

rhizoxin Rhizoxin is an antimitotic agent with anti-tumor activity. It is isolated from a pathogenic plant fungus ('' Rhizopus microsporus'') which causes rice seedling blight. Biosynthesis Rhizoxin is biosynthesised by ''Burkholderia rhizoxinica'', a ...

binding site).

National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. T ...

Definition of Maytansine
/ref> The monoclonal antibody binds specifically to a structure (usually a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

) occurring in a tumour, thus directing mertansine into this tumour. This concept is called

targeted therapy Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment ( pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy block ...

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. ADCs include: * Bivatuzumab mertansine *

Cantuzumab mertansine Cantuzumab mertansine (SB-408075; huC242-DM1) is an antibody-drug conjugate investigated to treat colorectal cancer and other types of cancer. It is a humanized monoclonal antibody, cantuzumab (huC242) linked to a cytotoxic agent, mertansine (DM1 ...

* Lorvotuzumab mertansine (IMGN901) for

CD56 Neural cell adhesion molecule (NCAM), also called CD56, is a homophilic binding glycoprotein expressed on the surface of neurons, glia and skeletal muscle. Although CD56 is often considered a marker of neural lineage commitment due to its discover ...

positive cancers, for example

multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, ane ...

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 as well as by the

World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...

(WHO) despite the fact that the linker contains only one

imide In organic chemistry, an imide is a functional group consisting of two acyl groups bound to nitrogen. The compounds are structurally related to acid anhydrides, although imides are more resistant to hydrolysis. In terms of commercial applicati ...

group according to the WHO. DM1 and its attachment via these linkers result from ImmunoGen Inc research. An example is: *

Trastuzumab emtansine Trastuzumab emtansine, sold under the brand name Kadcyla, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the cytotoxic agent DM1. Trastuzumab alone stops growth of can ...

(T-DM1), an anti-

HER2/neu Receptor tyrosine-protein kinase erbB-2 is a protein that in humans is encoded by the ''ERBB2'' gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The human protein is also frequently refer ...

antibody-drug conjugateImmunoGen: Trastuzumab-DM1
Emtansine mab structure coloured

References

{{reflist, 35em Experimental cancer drugs