RZ-11

RZ-11 is an investigational antibody-drug conjugate (ADC) developed for the treatment of hepatocellular carcinoma (HCC). It consists of a humanized monoclonal antibody targeting fibroblast growth factor receptor 4 (FGFR4) conjugated to the ferroptosis inducer sulfasalazine via a cathepsin B-cleavable GGFG peptide linker. FGFR4 is frequently overexpressed in HCC and correlates with poor survival, making it a viable therapeutic target. Upon binding to FGFR4 on the surface of tumor cells, the ADC is internalized via endocytosis. Within the lysosomal compartment, the GGFG linker is cleaved, releasing sulfasalazine into the cytosol. Sulfasalazine subsequently inhibits the System Xc- cystine/glutamate transporter, leading to glutathione depletion and the induction of iron-dependent lipid peroxidation, a process known as ferroptosis. Preclinical studies have demonstrated that RZ-11 specifically induces cell death in FGFR4-expressing HCC cells and exhibits robust anti-tumor activity in xenograft models.

Other names

anti-FGFR4-sulfasalazine ADCanti-FGFR-4-sulfasalazine ADCanti-FGFR 4-sulfasalazine ADCFGFR4-ADC-sulfasalazineFGFR-4-ADC-sulfasalazineFGFR 4-ADC-sulfasalazine