Maytansinoids

Maytansinoids

Catalog Product Name CAS Number Molecular Formula Molecular Weight
BADC-00852 Mc-Dexamethasone 1618096-56-2 C29H38FN3O6 543.63 g/mol
BADC-00357 Ansamitocin P-3 66584-72-3 C32H43N2O9Cl 635.14
BADC-00714 Maytansinol 57103-68-1 C28H37ClN2O8 565.06
BADC-00020 DM1-SMe 138148-68-2 C36H50ClN3O10S2 784.38
BADC-00086 Mertansine 139504-50-0 C35H48ClN3O10S 738.29
BADC-00087 Maytansinoid DM4 799840-96-3 C39H56ClN3O10S 780.37
BADC-00009 DM1-SMCC 1228105-51-8 C51H66ClN5O16S 1072.62
BADC-00189 Ansamitocin P 3' 66547-09-9 C32H43ClN2O9 635.14
BADC-00010 DM1-SPP 452072-20-7 C44H59ClN4O14S2 967.54
BADC-00011 DM4-SPDP 2245698-48-8 C45H61ClN4O14S2 981.57
BADC-00012 DM4-SPDB 1626359-62-3 C46H63ClN4O14S2 995.59
BADC-00017 DM4-SMCC 1228105-52-9 C54H72ClN5O16S 1114.69
BADC-00347 DM4 796073-69-3 C38H54ClN3O10S 780.37
BADC-00021 DM4-SMe 796073-68-2 C39H56ClN3O10S2 826.46
BADC-00022 DM3-SMe 796073-70-6 C38H54ClN3O10S2 812.43
BADC-00339 DM3 796073-54-6 C37H52ClN3O10S 766.34
BADC-00687 N-Me-L-Ala-maytansinol 77668-69-0 C32H44ClN3O9 650.16
BADC-00574 Lys-SMCC-DM1 1281816-04-3 C53H75ClN6O15S 1103.71
BADC-00600 Sulfo-PDBA-DM4 1461704-01-7 C42H60ClN3O15S3 978.58
BADC-00601 Mal-VC-PAB-DM1 1464051-44-2 C61H82ClN9O17 1248.81

As the chemical derivatives of Maytansine, Maytansinoids are tubulin inhibitors with the strongest known activities. It has strong inhibitory activities against various tumor cells and solid tumor systems. Since the greater toxic side effects when directly used in clinical treatment, Maytansinoids are commonly used as potent cytotoxic payloads in antibody-drug conjugates (ADCs). In the ADCs format, these potent Maytansinoids could be targeted to specific (diseased) cell types, thereby expanding their therapeutic window. Since that time, many other Maytansinoids have been developed as antibody payloads.

Chemical structure

Maytansinoids are nineteen-membered macrocyclic lactams with eight chiral carbon atoms and two trans-conjugated double bonds. Structure-activity-relationship studies had identified the C3 ester side chain as a critical element for antitumor activity of Maytansinoids. The Maytansinoids bearing the methyl group at C3 position with D configuration were about 100 to 400-fold less cytotoxic than their corresponding L-epimers toward various cell lines. Changing the configuration of C3 from α to β will result in the loss of anti-tumor activities of Maytansinoids. Furthermore, groups on hydrophobic side of macrocyclic lactam skeleton also have important influence on activities.

Mechanism of action

Maytansinoids compounds play an anti-tumor role mainly through the activities of tubulin inhibitors. Specifically, it can prevent the formation of microtubule bundles by bind to the vincristine site of tubulin β-subunit and competitively inhibit the binding of vincristine to tubulin (the inhibition constant of Maytansinoids is 0.4 x 10-6 M). This interaction arrest cells in G2/M phase and destroys the mitosis process of cell, which inhibit the growth of tumor cells. Maytansinoids not only has anti-tumor activity, but also can effectively inhibit other eukaryotes, such as protozoa, yeast, most fungi, insects and plants.

Application

Maytansinoids have significant activity on various tumor cell lines or solid tumors. Among them, Maytansine has significant inhibitory activity on Lewis lung cancer cells and B-16 melanoma mouse solid tumors, and has significant anti-leukemia activity on murine lymphocytic leukemia P-388 cells. Compounds with similar structure to Maytansine, such as Maytanpine, Maytanbutine and Normaytansine, also have similar activity profiles. Preclinical studies indicated that antibody Maytansinoid conjugates (AMCs) have significantly improved potential as anticancer agents compared with the unconjugated Maytansinoids. A recent trial on trastuzumab-DM1 (T-DM1), a Maytansinoid conjugated to the anti-human epidermal growth factor receptor 2 therapeutic antibody trastuzumab, showed good efficacy in metastatic breast cancer.

References

  1. Li, W.; et al. C3 ester side chain plays a pivotal role in the antitumor activity of Maytansinoids. Biochemical and Biophysical Research Communications, 2021, 566: 197-203.
  2. Porter, J.; et al. A highly potent maytansinoid analogue and its use as a cytotoxic therapeutic agent in gold nanoparticles for the treatment of hepatocellular carcinoma. Bioorganic & Medicinal Chemistry Letters, 2020, 30: 127634.
* Only for research. Not suitable for any diagnostic or therapeutic use.

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