tead-in-3

TEAD-IN-3 (compound I-177) is a potent inhibitor of the TEAD transcription factor, which can be used to study proliferative diseases such as cancer.

YAP-TEAD-IN-3 is an inhibitor of YAP TAZ-TEAD interactions with an IC50 of 9 nM for Avi-human TEAD (4217-434). YAP-TEAD-IN-3 inhibits YAP reporter gene expression (IC50 = 0.048 μM) and NCI-H2052 cell proliferation (IC50 = 0.048 μM).

pan-TEAD-IN-1 (Compound 3) is an orally active pan-inhibitor of TEAD, disrupting its interaction with coactivators YAP TAZ by targeting the palmitoylation site of TEAD. This inhibition leads to the downregulation of oncogene transcription, such as Ctgf and Cyr61, within the Hippo signaling pathway. Demonstrating outstanding efficacy, pan-TEAD-IN-1 has an IC50 of 0.36 nM for luciferase and 1.52 nM for H226 cells, along with favorable pharmacokinetic properties (AUC0–∞= 228.7 μg mL·min, T1 2= 183.9 min). The compound significantly inhibits tumor growth in xenograft models of TEAD-dependent cancers, indicating its potential for research in these cancer types.