|Catalog||Product Name||CAS Number||Molecular Formula||Molecular Weight|
|BADC-00189||Ansamitocin P 3'||66547-09-9||C32H43ClN2O9||635.14|
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.
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.
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.
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.