G3/4 anemia, neutropenia and peripheral neuropathy were consistently reported for MMAE ADCs, thrombocytopenia and hepatic toxicity for DM1, and ocular toxicity for MMAF. Safety profiles of MMAE, DM1, and DM4 ADCs differed between solid and hematologic cancers.

Ocular toxicity is one of the key off-target dose-limiting toxicities of ADCs containing the SPDB-DM4 linker-payload, such as cantuzumab ravtansine [165], mirvetuximab soravtansine [166], and coltuximab ravtansine [167], or the mc-MMAF linker-payload, such as belantamab mafodotin [119], AGS-16C3F [168], and SGN-75 [169].

The SPDB-DM4 ultimately releases neutral diffusible metabolites (DM4 and S-methyl-DM4), which have the potential for bystander killing of neighboring cells, while the mc-MMAF produces cysteine-mc-MMAF as the charged active metabolite within the cell, which does not have bystander effects.

Apr 23, 2023 · Elahere (mirvetuximab soravtansine-gynx) is a first-in-class ADC consisting of a folate receptor alpha (FRα)-conjugated antibody, a cleavable linker, and the maytansinoid payload DM4.

Maitansine (INN), or maytansine (USAN), is a cytotoxic agent. It inhibits the assembly of microtubules by binding to tubulin at the rhizoxin binding site. [1] . The maytansine binding site and binding mode has been characterized. [2] It is a macrolide of the ansamycin type and can be isolated from plants of the genus Maytenus. [1]

Mertansine, also called DM1 (and in some of its forms emtansine), is a thiol -containing maytansinoid that for therapeutic purposes is attached to a monoclonal antibody through reaction of the thiol group with a linker structure to create an antibody-drug conjugate (ADC). [1]

DM4, a structural analogue of maytansine, is a new thiol-containing and potent maytansinoid. DM4 is a cytotoxic maytansinoid drug. It is synthesized in order to link maytansinoids to antibodies via disulfide bonds.

Antibody-drug conjugate (ADC) is a relatively new class of therapeutic, which is generated by linking highly specific monoclonal antibodies (e.g., trastuzumab) to highly toxic chemical agents (e.g., DM1 or DM4) via different linker molecules [2, 3].

DM4, a structural analogue of maytansine, is a new thiolcontaining and potent maytansinoid. It was synthesized in order to link maytansinoids to antibodies via disulfide bonds. [1-3]DM4 is a cytotoxic maytansinoid drug. [4] Figure 1 DM4 particle.

DM4, a structural analogue of maytansine, is a new thiol-containing and potent maytansinoid. DM4 is a cytotoxic. maytansinoid drug. It is synthesized in order to link maytansinoids to antibodies via disulfide bonds. Maytansinoids inhibit. of microtubule dynamics resulting in a mitotic block and subsequent apoptotic cell death[1].