Apr 23, 2023 · In addition to the two approved drugs mentioned above, several Antibody-maytansinoid Conjugates have now entered clinical phase II/III, with warheads still focused on DM1/DM4, while targets have further expanded to FOLR1, CD37, CD56, CD19, CD138, Mesothelin, CA6, etc.

Most compounds in current clinical testing utilize either maytansine derivatives (DM1/DM4) or auristatins (MMAE/MMAF), which are both microtubule inhibitors. These typically induce apoptosis in cells undergoing mitosis by causing cell cycle arrest at G2/M.

For instance, severe anemia, neutropenia, and peripheral neuropathy were commonly reported for MMAE ADCs. For DM1 ADCs, grade 3/4 thrombocytopenia and hepatic toxicity are typically observed, and severe ocular toxicity is consistently reported for MMAF and DM4 ADCs.

We evaluated the effects on microtubule polymerization and dynamic instability of maytansine and two cellular metabolites (S-methyl DM1 and S-methyl DM4) of antibody-maytansinoid conjugates that are potent in cells at pM levels and that are active in tumor-bearing mice.

Jun 5, 2021 · Maytansine derivatives are mainly divided into two categories: DM1 and DM4. DM1 agents are highly potent maytansinoids (emtansine and mertansine) that have broad killing effects on non-Hodgkin lymphoma (NHL) xenografts in vivo . DM4 agents comprise soravtansine and ravtansine (e.g., coltuximab ravtansine), which can augment the bystander effect ...

DM1和DM4均为美登素的衍生物，美登素是一种是安莎霉素类的大环内酯，是一种微管抑制剂，其衍生物有DM1和DM4，区别在于与巯基连接的基团，DM1为 -CH2-CH2-S-，DM4则是-CH2-CH2-C (CH3)2-S-。 DM-1和DM-4的化合物结构均记载于专利US5416064A和US5208020A中。 2、DNA损伤剂类的payload. 1）SN-38. SN-38是拓扑异构酶I抑制剂伊立替康的活性代谢产物，该化合物记载于申请于1982年的专利US4473692A和US4545880A中。

Oct 1, 2023 · Derived DM1 and DM4, with methylthiopropionyl group, can be conjugated to the linker by disulfide bonds. DM1 and DM4 are the most commonly used two maytansine-like ADC payloads in clinical practical applications, such as Trastuzumab-SMCC-DM1, the first ADC drug based on maytansine derivatives approved for marketing ( ClinicalTrials.gov ...

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.

We evaluated the effects on microtubule polymerization and dynamic instability of maytansine and two cellular metabolites (S-methyl-DM1 and S-methyl-DM4) of antibody-maytansinoid conjugates that are potent in cells at picomolar levels and that are active in tumor-bearing mice.

As of September 2023, DM1 and DM4 are components of two clinically approved ADCs, trastuzumab emtansine and mirvetuximab soravtansin, respectively, and while the difference in their cytotoxic...