ADC-11

ADC-11 is an experimental antibody-drug conjugate (ADC) consisting of the anti-EGFR monoclonal antibody cetuximab conjugated to cyclopamine, a natural product inhibitor of the Hedgehog (HH) signaling pathway. Developed to overcome the poor pharmacokinetics and off-target effects of free cyclopamine, ADC-11 targets cells overexpressing the epidermal growth factor receptor (EGFR). Upon binding to EGFR and subsequent internalization, the conjugate utilizes an acid-cleavable linker to release cyclopamine within the endo-lysosomal compartment (pH ~5.5). The released payload then antagonizes the Smoothened (SMO) receptor, leading to the downregulation of GLI1 and GLI2 transcription factors. This targeted delivery induces apoptosis and inhibits proliferation in HH-active cancer cells, such as those found in melanoma, while potentially reducing systemic toxicity.

Other names

Cetuximab-cyclopamineCetuximab-cyclopamine ADCC-Cyclo