TEAD ligand-Linker Conjugate 3 (A536) is an IAP-recruiting bifunctional degrader (IPD) in the ALP2 series, specifically targeting TEAD1, with a degradation DC50 of 110 nM for human TEAD1 and a maximum degradation efficiency (Dmax) of 51%. This compound binds effectively to cIAP1 and induces its degradation (IC50=122 nM), while also possessing good cell permeability. It is composed of ALP2 target protein ligand and PROTA Clinker, making it suitable for PROTAC synthesis. A536 demonstrates dose-dependent inhibition of cell proliferation in Hippo pathway-dependent human malignant mesothelioma cells and downregulates the transcriptional expression of the TEAD1 downstream target gene CTGF. Additionally, A536 is useful for studying mechanisms in malignancies with abnormal Hippo pathway activation, particularly in NF2-mutant mesothelioma.

CIAP1:122 nM