Maytansinol
[CAS# 57103-68-1]

Identification

• Classification: API >> Inhibitor drug
• Name: Maytansinol
• Synonyms: Ansamitocin P 0; Antibiotic C 15003P; 3-O-De[2-(acetylmethylamino)-1-oxopropyl]maytansine
• Molecular Formula: C₂₈H₃₇ClN₂O₈
• Molecular Weight: 565.05
• CAS Registry Number: 57103-68-1
• EC Number: 680-675-1
• 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)O)C)\C)OC)(NC(=O)O2)O

Properties

• Solubility: Insoluble (2.2E^-3 g/L) (25 ºC), Calc.^*
• Density: 1.34±0.1 g/cm³ (20 ºC 760 Torr), Calc.^*
• Melting point: 205-207 ºC^**

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

^** Widdison, Wayne C.; Journal of Medicinal Chemistry 2006, V49(14), P4392-4408.

Safety Data

• Hazard Symbols: GHS05;GHS06;GHS07;GHS08 Danger
• Hazard Statements: H300-H301-H310-H311-H314-H315-H319-H330-H331-H340-H371
• Precautionary Statements: P203-P260-P261-P262-P264-P264+P265-P270-P271-P280-P284-P301+P316-P301+P330+P331-P302+P352-P302+P361+P354-P304+P340-P305+P351+P338-P305+P354+P338-P308+P316-P316-P318-P320-P321-P330-P332+P317-P337+P317-P361+P364-P362+P364-P363-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin corrosion	Skin Corr.	1B	H314
Acute toxicity	Acute Tox.	1	H300
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	2	H371
Acute toxicity	Acute Tox.	2	H331
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	1	H330
Germ cell mutagenicity	Muta.	1B	H340
Acute toxicity	Acute Tox.	1	H310
Acute toxicity	Acute Tox.	3	H311
Skin irritation	Skin Irrit.	2	H315

Discovory and Applicatios

Maytansinol is a naturally occurring compound first isolated from the bark of the East African shrub Maytenus serrata. Its discovery dates back to the 1970s when researchers identified its potent cytotoxic properties against cancer cells. The compound was initially investigated for its potential as a chemotherapeutic agent due to its ability to inhibit microtubule assembly, a crucial process for cell division.

Maytansinol and its derivatives, such as maytansine and DM1 (emtansine), have gained significant attention in the field of cancer therapy. Maytansinol itself has shown promise in preclinical studies for the treatment of various cancers, including breast, lung, and prostate cancer. However, its clinical use is limited due to its toxicity and poor solubility. Nonetheless, maytansinol serves as a valuable precursor for the development of antibody-drug conjugates (ADCs). ADCs combine the specificity of monoclonal antibodies with the cytotoxic effects of small-molecule drugs, allowing for targeted delivery of chemotherapy to cancer cells while minimizing systemic toxicity. Notably, the ADC trastuzumab emtansine (T-DM1) utilizes maytansinol derivative DM1 and has been approved for the treatment of HER2-positive breast cancer, demonstrating the therapeutic potential of maytansinol-based compounds in cancer therapy.

References

1985. Structure-activity relationships among maytansinoids in their effect on the European corn borer, Ostrinia nubilalis (H�bner). Journal of Chemical Ecology, 11(4).
DOI: 10.1007/bf00989561

2011. Combinatorial effect of maytansinol and radiation in Drosophila and human cancer cells. Disease Models & Mechanisms, 4(4).
DOI: 10.1242/dmm.006486

2021. C3 ester side chain plays a pivotal role in the antitumor activity of Maytansinoids. Biochemical and Biophysical Research Communications, 566.
DOI: 10.1016/j.bbrc.2021.05.071