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TCO-MMAE
- Development stage
- Preclinical
- Lead developer
- Shasqi
- Modality
- Peptides, Small Molecules
- Administration
- Intravenous
01
Overview
TCO-MMAE is a click chemistry-activated protodrug consisting of the potent cytotoxic agent monomethyl auristatin E (MMAE) modified with a trans-cyclooctene (TCO) group. Developed by Shasqi using its Click Activated Protodrugs Against Cancer (CAPAC™) platform, TCO-MMAE is designed to remain inactive and stable in systemic circulation, thereby reducing off-target toxicity. The drug is selectively activated at the tumor site through an inverse electron-demand Diels-Alder (IEDDA) reaction with a tumor-localized tetrazine (Tz) activator, such as a Tz-modified biopolymer or an antigen-targeted Fab-Tz conjugate. This localized activation restores the cytotoxic activity of MMAE, which subsequently inhibits tubulin polymerization, leading to cell cycle arrest and apoptosis. Preclinical studies have demonstrated efficacy in models of non-Hodgkin’s lymphoma, renal adenocarcinoma, and HER2-positive gastric cancer.
- Other names
- trans-cyclooctene-monomethyl auristatin E
02
Targets
Tz-carrier (Tetrazine functional group on tumor-localized carrier)TUBB (Tubulin (alpha and beta subunits))
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