tead

MYF-01-37 (1-[3-Methyl-3-[3-(trifluoromethyl)anilino]pyrrolidin-1-yl]prop-2-en-1-one) is a novel covalent TEAD inhibitor.

VT-105 is a potent and selective TEAD autopalmitoylation inhibitor that hinders proliferation and tumor growth in NF2-deficient mesotheliomas.

GNE-7883 is an inhibitor targeting TEAD transcription factor, inhibits cell proliferation and suppresses YAP/TAZ activation, and can be used to study YAP/TAZ-dependent tumors.

TED-347 is an irreversible and covalent inhibitor of TEAD4-Yap1 protein-protein interaction(EC50 of 5.9 μM), and inhibits glioblastoma cell viability.

MGH-CP1 is a potent and selective inhibitor of TEAD palmitoylation, demonstrating dose-dependent and potent inhibition of TEAD2/4 auto-palmitoylation in vitro with IC50 values of 710 nM and 672 nM, respectively.

K-975 is a highly selective, orally active TEAD inhibitor, effectively inhibiting protein-protein interactions between TEAD and YAP1/TAZ.

YAP-TEAD-IN-3 (IAG933) belongs to small molecule inhibitors and is a TEAD-targeted YAP/TAZ-TEAD protein-protein interaction inhibitor (IC50 = 9 nM) with oral activity and selective inhibitory capability against all four TEAD isoforms. This compound is used in antitumor and pro-apoptosis research.

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.

YAP/TEAD-IN-1 (compound 4) is a potent inhibitor of YAP and TEAD, exhibiting antioxidant properties. It demonstrates antiproliferative effects on tumor cells while showing minimal cytotoxic activity towards normal human cells.

TEAD-IN-1 (Compound 2) is an effective inhibitor of TEAD auto-palmitoylation with an IC50 of 603 nM. It enhances the interaction between TEAD and VGLL4, while diminishing the interaction between YAP and TEAD. TEAD-IN-1 is applicable for cancer research.

TEAD-IN-19 (Compound 1l) is a transcriptional inhibitor of TEAD, showing inhibition rates of 38.5%, 36.2%, 57.8%, and 71.3% for TEAD1, TEAD2, TEAD3, and TEAD4, respectively, at 10 μM. It exhibits strong antiproliferative and antimigratory effects on prostate cancer cell lines and significantly reduces the expression of TEAD-regulated downstream genes. TEAD-IN-19 holds potential for research in the field of cancer therapeutics.

TEAD-IN-20 is a TEAD inhibitor with IC50 values of 0.021 μM in TEAD4 FRET and 0.044 μM in TEAD4 MCF7-Tead cell lines. It has potential applications in cancer research.

TEAD-IN-9 (compound 17) is a TEAD1 inhibitor with an IC50 of 0.29 μM. It targets the palmitoyl pocket of TEAD, effectively inhibiting the binding of YAP-TEAD and blocking the transcriptional function of YAP-TEAD.

PROTACTEAD degrader-1 (Compound 27) is a PROTAC degrader of the transcriptional enhanced associate domain (TEAD). It selectively degrades Flag TEAD2 through a ubiquitin-protease-dependent mechanism, with a DC50 of 54.1 nM in 293T cells. This compound inhibits the proliferation of NF2-deficient NCI-H226 cells, showing an IC50 of 0.21 μM, and modulates the expression of yes-associated protein (YAP) target genes.

TEAD-IN-14 (75a) is an orally active TEAD inhibitor with an IC50 value of less than 100 nM and a half-life of 2.3 hours in mice.

TEAD-IN-16 (compound BC-011) is a potent inhibitor of TEAD, with an IC50 of 72.43 μM. This compound plays a significant role in cancer research.

TEAD-IN-21 is a potent, orally bioavailable pan-TEAD inhibitor with an IC50 of 3 nM. It effectively suppresses proliferation in Huh-7 cells and selectively downregulates TEAD-dependent downstream genes. In mouse models with liver cancer-derived tumor xenografts, TEAD-IN-21 leads to tumor regression. This compound is applicable for hepatocellular carcinoma (HCC) research.

TEAD-IN-22 (compound I) is a TEAD inhibitor with potential applications in cancer and fibrosis research.

YAP/TEAD-IN-2 (Compound T-1) is an inhibitor of YAP/TEAD. This compound suppresses luciferase activity driven by YAP/TEAD in 293T cells and exhibits strong antiproliferative effects on human pleural mesothelioma NCI-H226 cells. YAP/TEAD-IN-2 is applicable for studying diseases associated with disruptions in the Hippo pathway, particularly cancer.

TEAD-IN-23 (Compound 22) is a potent pan-TEAD inhibitor with an IC50 of 10 nM. It exhibits strong antiproliferative activity against NCI-H226 and MSTO-211H cell lines. In the MSTO-211H xenograft tumor model, TEAD-IN-23 causes complete tumor regression. This compound is suitable for research on mesothelioma and hepatocellular carcinoma.

TEAD-IN-24 (Example 65) is a TEAD inhibitor with anticancer activity against non-small cell lung cancer.

PROTACTEAD degrader-2 (Compound 31) is a potent TEAD1 PROTAC degrader with a DC50 of 0.6 nM. It inhibits the YAP/TAZ-TEAD interaction with an IC50 of 1.8 nM and shows significant selective inhibitory activity against YAP-dependent cancer cells, effectively suppressing YAP-mediated transcriptional activity. This compound is applicable in mesothelioma and glioma research.

TEADligand-Linker Conjugate 1 is a synthetic target protein ligand-linker conjugate, designed for the synthesis of PROTACs like PROTACTEADdegrader-2. PROTACTEADdegrader-2 serves as a potent TEAD1 PROTAC degrader with anti-cancer properties.

YAP/TAZ-TEAD-IN-3 is an inhibitor of YAP/TAZ-TEAD interactions with an IC50 of 1.8 nM. It can be utilized as a TEAD1 ligand for constructing PROTACs, such as PROTAC TEAD degrader-2.