YAP/TAZ Inhibitor

VT3989 is an orally active pan-TEAD autopalmitoylation inhibitor that modulates the Hippo signaling pathway. VT3989 directly binds to TEAD transcription factors to block their palmitoylation modification, thereby disrupting the formation of YAP/TAZ-TEAD complexes and inhibiting downstream oncogenic transcriptional activity. VT3989 effectively inhibits the growth of NF2-deficient schwannoma and meningioma cells and reverses the Schwann cell phenotype. In addition, VT3989 exerts a synergistic effect when combined with Osimtinib (HY-15772) in EGFR-mutant non-small cell lung cancer models, significantly delaying tumor recurrence and prolonging survival. VT3989 can be used for the research of epithelioid hemangioendothelioma, malignant pleural mesothelioma, type 2 neurofibromatosis and related advanced solid tumors.

Ki16425 (Debio 0719) is a subtype-selective, competitive antagonist of the EDG-family receptors, LPA1 and LPA3 with K_is of 0.34 μM and 0.93 μM, respectively. Ki16425 (Debio 0719) reduces the LPA-induced activation of p42/p44 MAPK. Ki16425 can also inhibit LPA-induced dephosphorylation of Yes-associated protein (YAP)/TAZ in HEK293A cells.

YAP/TAZ inhibitor-1 is a YAP/TAZ inhibitor extracted from patent WO2017058716A1, Compound 1, has an IC₅₀ of <0.100 μΜ in firefly luciferase assay.

YAP-TEAD-IN-1 TFA is a potent and competitive peptide inhibitor of YAP-TEAD interaction (IC₅₀=25 nM). YAP-TEAD-IN-1 TFA is a 17mer peptide and shows a higher the binding affinity to TEAD1 (K_d=15 nM) than YAP (50-171) (K_d= 40 nM).

MY-1576 is a FAK inhibitor with an IC₅₀ of 8 nM. MY-1576 can activate the Hippo pathway, thereby blocking the regulation of YAP/TAZ. MY-1576 also effectively inhibits tumor growth in the KYSE30 xenograft mouse model, demonstrating good safety, and effectively downregulates the autophosphorylation of FAK and the levels of YAP/TAZ in vivo.

YAP/TAZ inhibitor-4 (Compound 45) is an inhibitor of YAP/TAZ, exhibiting TEAD transcriptional activation inhibitory activity by suppressing the binding of YAP or TAZ to TEAD.