Maytansinoid Synthesis Service

With years of experience and our advanced "DrugLnk" synthetic chemistry platform, Creative Biolabs has established a comprehensive service program for antibody-drug conjugates (ADCs) developments. Our scientists can help design and provide clients with customized antibody-drug conjugates (ADCs) containing different maytansinoid variants using optimized linkers and suitable conjugation strategies.

Maytansine and its derivatives (named as maytansinoids in general) are members of the ansamycins superfamily and contains a 19-member macrocyclic lactams attached to a chlorinated benzene. Maytansine is originally isolated from an Ethiopian shrub Maytenus ovatus and exerts extremely high anti-mitotic potency. Maytansinoids are microtubule-targeting agents that share same binding site with vinca and function by depolymerizing microtubules and arresting cells in the mitosis stage. Maytansinoids reveal over 100-fold elevated cytotoxicity in cells than vinca alkaloids, making them suitable candidates in anti-cancer therapies utilizing tissue-specific drug delivery strategies, particularly as ADCs. The form of ADC significantly increases the therapeutic window of maytansinoids comparing to the free drugs, enabling the usage of an otherwise highly toxic drug in cancer treatments.

Fig.1 Chemical structures of maytansine and its derivatives.^1,3

Maytansine Mode of Action (MOA)

As tubulin inhibitors, maytansinoids and its analogues inhibit the assembly of microtubules by binding to tubulin at or near the vinblastine-binding site. They can decrease microtubule dynamic instability and cause mitotic arrest in cells, similar to the MOA of vinblastine. Furthermore, maytansinoids exert cytotoxicity against a number of tumor cell lines and inhibit tumor growth in vivo. However, in human clinical trials, maytansine showed a small therapeutic window due to its neurotoxicity and harmful effects on the gastrointestinal tract. In the form of an antibody-drug conjugate, the toxicity as well as the side-effects caused by free maytansine could be reduced. By far, numerous attempts have been made to conjugate maytansine and its analogues to an antibody. Chemical modifications on maytansinoids are common to facilitate the conjugation, for instance the native N-acetyl group in many disulfide-containing maytansinoids are often replaced with methyldithio-propanoyl group for this very purpose.

Fig.2 Maytansine mode of action. ^1,3

Antibody-maytansinoid Conjugates

Several antibody-maytansinoid conjugates have emerged as good anti-cancer candidates. Trastuzumab-MCC-DM1, an ADC in which maytansinoid was conjugated to the anti-HER2 antibody trastuzumab showed superb efficacy against metastatic breast cancer. Chemical versatility of maytansinoids enables the use of various linkers in antibody-maytansinoid conjugate preparation: for instance, T-DM1 uses a non-cleavable thioether-based linker.

Fig.3 Maytansine conjugates for cancer treatments. ^2,3

Fig.4 Chemical structure of the most common linkers. ^1,3

Currently, several antibody-maytansinoid conjugates are under evaluation in clinical trial stages while many more are under active development in pre-clinical pipelines. Based on our well-established "DrugLnk" synthesis platform and extensive experience in ADC preparation, Creative BioLabs can help create unique antibody-maytansinoid conjugates with optimized linkers to meet your requirements. In the meantime, Creative BioLabs also provides various other ADC-related services. Please feel free to contact us for more information and a detailed quote regarding your ADC design and production.

References:

1. Perra, Matteo, et al. "Maytansinoids in cancer therapy: advancements in antibody–drug conjugates and nanotechnology-enhanced drug delivery systems." Discover Oncology 16.1 (2025): 73.
2. Zafar, Sameen, et al. "New insights into the anticancer therapeutic potential of maytansine and its derivatives." Biomedicine & Pharmacotherapy 165 (2023): 115039.
3. Distributed under Open Access License CC BY 4.0, without modification.