Mertansine
[CAS# 139504-50-0]

Identification

• Classification: API >> Inhibitor drug
• Name: Mertansine
• Synonyms: DM 1; Maytansinoid DM 1;N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)maytansine; [(1S,2R,3S,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] (2S)-2-[methyl(3-sulfanylpropanoyl)amino]propanoate
• Molecular Formula: C₃₅H₄₈ClN₃O₁₀S
• Molecular Weight: 738.29
• Protein Sequence: CA
• CAS Registry Number: 139504-50-0
• EC Number: 641-051-4
• SMILES: C[C@@H]1[C@@H]2C[C@]([C@@H](/C=C/C=C(/CC3=CC(=C(C(=C3)OC)Cl)N(C(=O)C[C@@H]([C@]4([C@H]1O4)C)OC(=O)[C@H](C)N(C)C(=O)CCS)C)C)OC)(NC(=O)O2)O

Properties

• Solubility: Insoluble (2.4E^-4 g/L) (25 °C), Calc.^*
• Density: 1.33±0.1 g/cm³ (20 °C 760 Torr), Calc.^*
• Melting point: 190-192 °C (decomp)^**

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2014 ACD/Labs)

^** Widdison, Wayne C.

Safety Data

• Hazard Symbols: GHS05;GHS06;GHS08 Danger
• Risk Statements: H300-H310-H314-H340-H350-H360-H370
• Safety Statements: P203-P260-P262-P264-P270-P280-P301+P316-P301+P330+P331-P302+P352-P302+P361+P354-P304+P340-P305+P354+P338-P308+P316-P316-P318-P321-P330-P361+P364-P363-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	1	H310
Skin corrosion	Skin Corr.	1B	H314
Reproductive toxicity	Repr.	1B	H360
Specific target organ toxicity - single exposure	STOT SE	1	H370
Germ cell mutagenicity	Muta.	1B	H340
Carcinogenicity	Carc.	1B	H350
Acute toxicity	Acute Tox.	2	H300
Acute toxicity	Acute Tox.	1	H300

Discovery and Applications

N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)maytansine, commonly referred to as DM1, was discovered in the late 1970s by researchers at Takeda Chemical Industries in Japan. It was isolated from the bacterium Streptomyces lavendulae.

DM1 serves as a potent cytotoxic payload in antibody-drug conjugates (ADCs) for targeted cancer therapy. By disrupting microtubule assembly, DM1 induces cell cycle arrest and apoptosis. ADCs incorporating DM1, such as ado-trastuzumab emtansine (Kadcyla), have received FDA approval for treating HER2-positive breast cancer. These conjugates precisely deliver the cytotoxic payload to cancer cells, minimizing systemic toxicity. Beyond breast cancer, DM1 is under investigation for its potential in treating various cancers, including lymphomas and solid tumors, either as a monotherapy or in combination regimens.

References

1977. Ansamycins. Chemistry, biosynthesis and biological activity. Topics in current chemistry.
DOI: 10.1007/bfb0048448

2024. The Efficacy and Safety of Folate Receptor α‐Targeted Antibody‐Drug Conjugate Therapy in Patients With High‐Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers: A Systematic Review and Meta‐Analysis. Cancer Medicine.
DOI: 10.1002/cam4.70392

2024. Synthesis and evaluation of antibody-drug conjugates with high drug-to-antibody ratio using dimaleimide-DM1 as a linker-payload. Bioorganic Chemistry.
DOI: 10.1016/j.bioorg.2024.107504