tead

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

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-TEAD-IN-1 TFA, a competitive inhibitor of the YAP–TEAD interaction (IC50: 25 nM), exhibits higher binding affinity to TEAD1 (Kd: 15 nM) compared to YAP (50-171) (Kd: 40 nM).

YAP-TEAD-IN-1 acetate is an effective and competitive inhibitor of YAP–TEAD interaction with an IC50 of 25 nM.

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

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].

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.

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.

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.

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.

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 is a competitive inhibitor of YAP–TEAD interaction (IC50: 25 nM) and exhibits higher binding affinity to TEAD1 (Kd: 15 nM) compared to YAP (50-171) (Kd: 40 nM).

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].

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-12 (58B), a potent TEAD inhibitor, demonstrates oral activity, exhibiting an IC 50 of <100 nM and a half-life of 3.6 hours in mouse.

TEAD-IN-13 (64) serves as an orally active inhibitor of TEAD, exhibiting an IC 50 of <100 nM and possessing a half-life of 3.2 hours in mice.

DC-TEADin02 is an inhibitor of TEAD auto palmitoylation (IC50 = 197 nM). DC-TEADin02 can be in studies about development, regeneration, and tissue homeostasis.

DC-TEADin04 exhibits weak inhibitory activity against TEAD4 palmitoylation [1].

Verteporfin (BPD-MA) is a YAP inhibitor that inhibits YAP-TEAD interactions. Verteporfin is also a photosensitizer used in photodynamic therapy. Verteporfin also induces apoptosis and inhibits autophagy.

VT104 is a potent and orally active YAP TAZ inhibitor for cancer research. VT104 blocks palmitoylation of endogenous TEAD1 and TEAD3 proteins.

VT107 is a potent pan-TEAD autopalmitoylation inhibitor. VT-107 can be used in cancer therapy research.[1]