Maytansinol Property

Melting point:

205-207℃

Boiling point:

835.8±65.0 °C(Predicted)

Density 

1.34±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

Chloroform (Slightly), Methanol (Slightly)

form 

Solid

pka

9.89±0.70(Predicted)

color 

Off-White to Orange

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H340May cause genetic defects

Precautionary statements

P201Obtain special instructions before use.

P202Do not handle until all safety precautions have been read and understood.

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P310IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P308+P313IF exposed or concerned: Get medical advice/attention.

P312Call a POISON CENTER or doctor/physician if you feel unwell.

P321Specific treatment (see … on this label).

P330Rinse mouth.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P405Store locked up.

P501Dispose of contents/container to..…

Maytansinol Chemical Properties,Usage,Production

Description

Maytansinol (Ansamitocin P-0) is an inhibitor of microtubule assembly that induces microtubule disassembly in vitro.

Uses

Maytansinol is used in the preparation of site-specific trastuzumab maytansinoid antibody-drug conjugates with improved therapeutic activity. References Pillow, T.H., et. al.: J. Med. Chem., 57, 7890 (2014)

Biological Activity

Maytansinol is an ansamacrolide originally isolated from P. verrucose that has antimitotic and anticancer activities. It inhibits polymerization and induces depolymerization of bovine brain tubulin with EC50 values of 12 and 43 μM, respectively. Maytansinol inhibits sea urchin egg mitosis when used at a concentration of 10 μM and decreases proliferation of KB nasopharyngeal cancer cells (EC50 = 0.19 μg/ml).

Mode of action

Maytansinol (1 b) was first obtained by Kupchan et?al. both by isolation from Putterlickia verrucose and chemical removal of the acyl group from the hydroxy group at the C3 position. It showed weaker inhibitory activity on tubulin polymerization than maytansine, thus implying that the ester moiety at the C3 position of ansamitocins, maytansine, and maytansinoids plays an important role for biological activity and cell permeability. In fact, it has just recently been found that the carbonyl oxygen atom of the ester moiety forms a strong intramolecular interaction with the hydroxy group at position 9, fixing the bioactive conformation. Maytansinol has been regarded as a valuable precursor because acylation allows the preparation of both natural and new semisynthetic maytansinoids, differing in the ester side-chain substituents (Scheme 1). The acylation reaction of maytansinol is a crucial step in the preparation of maytansinoid ADCs or nanoparticles, constituting an uprising class of targeted cancer therapeutics. A few attempts to conjugate maytansinoids to peptides by this reaction have also been made very recently. Furthermore, considering that the maytansine binding site is one of the most recently identified and least explored on tubulin, acylation of maytansinol may serve for the preparation of useful molecular probes to better understand the structure-activity relationships of maytansinoids or to identify new maytansine-site ligands.

Structure of maytansine (1 a), maytansinol (1 b), and the generic acylation reaction of maytansinol.