Val-Cit-MMAF

A key ADC payload variant that pairs the protease-sensitive Val-Cit dipeptide linker with monomethyl auristatin F (MMAF), a polar microtubule inhibitor. The anionic C-terminal phenylalanine residue of MMAF confers reduced cell membrane permeability, limiting the cytotoxicity of free toxin to bystander cells. This bystander effect profile, combined with efficient cathepsin B-triggered release, makes the Val-Cit-MMAF construct particularly suitable for targeting solid tumors and antigens with heterogeneous expression, as exemplified by the ADC glembatumumab vedotin.

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