What's DM1, DM1-SMCC?
DM1 is abbr. of N2’-Deacetyl-N2’-(3-mercapto-1-oxopropyl)-maytansine, which is a maytansinoid cytotoxic agent used in trastuzumab emtansine and additional antibody-drug conjugates (ADC) in development.
DM1-SMCC, also called SMCC-DM1. It’s DM1 linked with SMCC (4-(3-mercapto-2,5-dioxo-1-pyrrolidinylmethyl)-cylohexanecarboxylic acid) linker. DM1-SMCC can react with amino group in MAB(monoclonal antibodies) directly with SMCC.
Structure of DM1 and DM1-SMCC:
Please refer to: DM1 | Tubulin-Binders
Please refer to: DM1-SMCC | Tubulin-Binders
DM1 Synonyms: N2' -deacetyl-N2' -(3-Mercapto-1-oxopropyl)-Maytansine; Maytansinoid DM 1
Toxicity of DM1:
IC50 of proliferation/viability of tumor cell lines are in the range of 10-10–10-12 M for DM1/DM4 maytansinoid derivatives.
DM1 mechanism of action:
DM1, and other Maytansine analogs are a microtubule-targeted drug that binds to tubulin at the vinca binding site, it can depolymerize microtubules and arrest cells in mitosis.
FDA approved ADCs drugs with DM1:
Kadcyla ® (ado-trastuzumab emtansine or T-DM1, Genentech) is an ADC comprised of trastuzumab conjugated through lysines to DM1, via a non-cleavable thioether linker (N-succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate, SMCC), with an average DAR of 3.5. The conjugate is abbreviated T-DM1.
The FDA approval of Kadcyla ® in 2013. Kadcyla ® Glossary is approved to treat HER2-positive breast cancer that has spread to other parts of the body (metastatic breast cancer) after prior treatment with trastuzumab (Herceptin) and a taxane. Prior treatment could have been for the initial treatment of breast cancer or for the treatment of cancer that had spread to other parts of the body. Trastuzumab alone stops growth of cancer cells by binding to the HER2/neu receptor, whereas DM1 enters cells and destroys them by binding to tubulin. Because the monoclonal antibody targets HER2, and HER2 is only over-expressed in cancer cells, the conjugate delivers the toxin specifically to tumor cells.
Commercial Availability of DM1:
DM1 and DM1-SMCC(SMCC-DM1) are commercial available from ALB Technology.
ALB Technology Limited is a professional ADCs drugs and linkers supplier. ALB Technology Limited's featured ADCs products include MMAE, MMAF, DM1, DM1-SMCC, Maytansinol, Fmoc-Val-Cit-PAB-MMAE, Fmoc-Val-Cit-PAB-MMAF, MC-Val-Cit-PAB-MMAE, MC-Val-Cit-PAB-MMAF,Val-Cit-PAB, Fmoc-Val-Cit-PAB, Fmoc-Val-Cit-PAB-PNP ect.