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Maytansinoid

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.

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Maytansinoid

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  1. Maytansinoid https://www.creative-biolabs.com/adc

  2. Maytansine • 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.

  3. Chemical structures of maytansine and its derivatives. Both DM1 and DM4 have been used as payloads for ADC development (Mol. Cancer Ther, 2010).

  4. CONTENTS Maytansine Mode of Action (MOA) 1 Antibody-maytansinoid Conjugates 2

  5. 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. Maytansine Mode of Action (MOA) 1

  6. Maytansine mode of action. Maytansine binds to tubulin and decrease microtubule dynamic instability, arresting the cells in the mitosis stage (Nat. Rev. Mol. Cell Biol., 2015)

  7. Several antibody-maytansinoid conjugates have emerged as good anti-cancer candidates. T-DM1 (trastuzumab-MCC-DM1), an ADC in which maytansinoid was conjugated to the anti-HER2 antibody trastuzumab showed superb efficacy against metastatic breast cancer while lorvotuzumab mertansine (huN901-SPP-DM1), a CD-56 targeting ADC, has also revealed hopeful results in solid and liquid tumors that express CD56. • 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, while lorvotuzumab mertansine uses a disulfide-based cleavable linker. Antibody-maytansinoid Conjugates 2

  8. Antibody-maytansinoid conjugates for cancer treatments. Maytansinoids were conjugated with lorvotuzumab (left) or trastuzumab (middle) via linkers bearing different release mechanisms (Mol Cancer Ther, 2010). Cleavable linkers undergo distinguished metabolism routes than non-cleavable linkers once internalized (right, Bioconjugate Chem, 2011).

  9. Contact us 45-1 Ramsey Road, Shirley, NY 11967, USA Tel: 1-631-619-7922 Fax: 1-631-207-8356 Email: marketing@creative-biolabs.com

  10. THANKS

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