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cetuximab-cyclopamine
- Development stage
- Preclinical
- Lead developer
- University of Parma
- Modality
- Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
- Administration
- Intravenous
01
Overview
ADC-16 is an experimental antibody-drug conjugate (ADC) composed of the anti-EGFR monoclonal antibody **cetuximab** covalently linked to **cyclopamine**, a natural product inhibitor of the Hedgehog (HH) signaling pathway. It is designed to selectively deliver cyclopamine into cancer cells that overexpress the epidermal growth factor receptor (EGFR) and exhibit HH pathway activation, such as certain melanoma cells. The ADC utilizes an acid-cleavable linker that remains stable in plasma but releases the cyclopamine payload within the acidic environment of the endo-lysosomal compartment (pH 5.5) following internalization. Once released, cyclopamine inhibits **Smoothened (SMO)**, leading to the downregulation of GLI1 and GLI2 transcription factors and the induction of apoptosis. This targeted delivery approach aims to overcome the unfavorable pharmacokinetics and off-target toxicities that have historically limited the clinical utility of systemic cyclopamine.
- Other names
- cetuximab-cyclopamine conjugate
02
Targets
EGFR (Epidermal growth factor receptor)SMO (Smoothened)
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