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 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).

YAP TAZ-TEAD-IN-2 (Compound 51) is a YAP TAZ-TEAD inhibitor that disrupts the interaction between YAP TAZ and TEAD. It inhibits the transcriptional activity of TEAD with an IC50 of 1.2 nM. Additionally, YAP TAZ-TEAD-IN-2 suppresses the expression of target genes (Cyr61, CTGF, AXL, and Survivin) and the proliferation of breast cancer cells.

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-2 is a potent and bifunctional TEAD inhibitor that binds to both TEAD proteins and E3 ubiquitin ligases or degradation-inducing motifs to induce TEAD protein degradation via the ubiquitination pathway, with anticancer and antiproliferative potential.

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-2 (compound 6) is a potent inhibitor of the YAP-TEAD protein-protein interaction (PPI), with an inhibitory concentration 50 (IC50) value of 2.7 nM [1].

TEAD-IN-6 (Example 11-1) is a TEAD modulator that inhibits the YAP1 TAZ-TEAD interaction and has applications in cancer research [1].

TM2 TEAD inhibitor, a robust and reversible inhibitor of the TEA domain transcription factor, presents dual inhibitory concentrations (IC50) of 38 nM for TEAD4 auto-palmitoylation and 156 nM for TEAD2 palmitoylation. It effectively blocks the TEAD-YAP association and their transcriptional activities, leading to significant antiproliferative effects in YAP-dependent cancer cell lines, both as a standalone agent and in combination with a MEK inhibitor. Additionally, it impedes YAP-dependent liver organoid growth ex vivo.

TEAD-IN-10 (compound 15), a covalent inhibitor, exhibits selective and potent inhibitory activity against TEAD1 (IC 50 =14 nM), TEAD2 (IC 50 =179 nM), and TEAD3 (IC 50 =4 nM). This compound is utilized in cancer research [1].

TEAD ligand 1 is a ligand for the target protein TEAD. TEAD ligand 1 can be utilized in the synthesis of the PROTACTEAD degrader-1.