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YZ-6
- Development stage
- Preclinical
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
- Administration
- Intraperitoneal
01
Overview
YZ-6 is a proteolysis-targeting chimera (PROTAC) designed to selectively degrade Yes-associated protein (YAP), a key transcriptional coactivator in the Hippo signaling pathway that is historically challenging to target due to its intrinsically disordered nature. Structurally, YZ-6 consists of the YAP binder NSC682769 linked to a von Hippel-Lindau (VHL) E3 ligase ligand. By recruiting the VHL E3 ubiquitin ligase complex, YZ-6 induces rapid and sustained proteasomal degradation of YAP, as well as its paralog TAZ. This action effectively inhibits YAP nuclear localization and curtails YAP/TEAD-mediated transcription. YZ-6 has demonstrated potent antiproliferative and pro-apoptotic effects in cancer cell lines, including Huh7 hepatocellular carcinoma and NCI-H226 mesothelioma, and has shown anti-fibrotic potential by attenuating biliary and liver fibrosis in preclinical mouse models.
- Other names
- PROTAC YAP degrader-1YAP degrader YZ-6YAP PROTAC YZ-6
02
Targets
VHL (Von Hippel–Lindau tumor suppressor protein)YAP1 (YES-associated protein–transcriptional enhancer factor domain complex)
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