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TEAD central pocket palmitoylation inhibitor
- Development stage
- Preclinical
- Lead developer
- AstraZeneca
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
TEAD central pocket palmitoylation inhibitors (CPIs) are a class of small molecule therapeutics designed to target the Hippo signaling pathway. These compounds bind to the highly conserved hydrophobic 'central pocket' of TEAD transcription factors (TEAD1, TEAD2, TEAD3, and TEAD4). This binding prevents the auto-palmitoylation of a conserved cysteine residue, a post-translational modification essential for TEAD structural stability and its ability to bind co-activators YAP and TAZ. By disrupting the formation of the transcriptionally active YAP/TAZ-TEAD complex, CPIs inhibit the expression of genes that promote cell proliferation, survival, and resistance to therapy. AstraZeneca and other developers are investigating TEAD CPIs as both monotherapies and in combination with other targeted agents, such as KRAS inhibitors, to treat various solid tumors including non-small cell lung cancer (NSCLC) and pancreatic cancer.
- Other names
- TEAD palmitoylation inhibitorTEAD central pocket inhibitor
02
Targets
TEAD (TEAD family)
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