YAP

Verteporfin is a small molecule that inhibits TEAD, YAP association and YAP-induced liver overgrowth. It is also a potent second-generation photosensitizing agent derived from porphyrin.

Peptide 17 is a inhibitor of this YAP-TEAD protein-protein interaction which has potential usage in treatment of YAP-involved cancers with IC50 of 25nM.

CIL56 (CA3) is a potent inhibitor of YAP1/TEAD transcriptional activity, selectively targeting YAP1-high, therapy-resistant esophageal adenocarcinoma cells with cancer stem cell (CSC) characteristics. It induces ferroptosis through iron-dependent reactive oxygen species (ROS) generation, offering a novel approach for overcoming resistance in aggressive tumors.

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.

MYF-01-37 is a novel covalent inhibitor of TEAD targeting Cys380.

PY-60 is a potent and selective small-molecule activator of YAP transcriptional activity that targets annexin A2 (ANXA2) with a dissociation constant (Kᴅ) of 1.4 µM. By directly binding to ANXA2, PY-60 antagonizes its inhibitory regulation of YAP, thereby enhancing YAP-dependent gene expression and promoting transcriptional activation within the Hippo signaling pathway.

Cytochalasin D (also known as Zygosporin A) is a cell-permeable fungal metabolite and a potent inhibitor of actin polymerization. It binds to G-actin, thereby disrupting the G-actin–cofilin interaction and preventing cofilin association with F-actin. Through this mechanism, Cytochalasin D reduces both actin polymerization and depolymerization rates in living cells, leading to profound effects on cytoskeletal organization and cell morphology. In addition, Cytochalasin D suppresses exosome release, consequently decreasing survivin levels within the tumor microenvironment. It also promotes phosphorylation and cytoplasmic retention of YAP, implicating it in the regulation of mechanotransduction and tumor cell signaling.

PROTAC YAP degrader-1 (compound YZ-6) is a bifunctional molecule designed to selectively degrade Yes-associated protein (YAP), a key effector of the Hippo signaling pathway involved in cell proliferation, survival, and tumorigenesis. In addition to promoting proteasomal degradation of YAP, it also inhibits YAP's nuclear localization, thereby impairing its transcriptional co-activator functions.YZ-6 is composed of two main components:Target protein ligand: NSC682769 and E3 ubiquitin ligase recruiter with linker: (R,S,R)-AHPC-PEG2-C2-Boc which recruits the VHL E3 ligase complex. The linker used in the PROTAC design is Acid-PEG2-C2-Boc, facilitating optimal spatial orientation for ternary complex formation. The demethylated analog Demethyl-NSC682769 serves as a target ligand activity control. PROTAC YAP degrader-1 represents a novel tool for functional YAP inhibition and offers potential therapeutic applications in YAP-driven cancers and fibrotic diseases.

IAG933 is a potent YAP-TEAD inhibitor that targets the YAP/TAZ-TEAD interaction, demonstrating significant anti-tumor effects by promoting apoptosis in cancer cells. With an IC50 value of 9 nM against Avi-human TEAD4217-434, IAG933 serves as a valuable tool for studies investigating the YAP signaling pathway and its role in oncogenesis. Its oral bioavailability further enhances its utility in in vivo research applications focused on cancer therapeutics.

VT3989 is a potent YAP/TAZ inhibitor, targeting the essential Hippo signaling pathway regulators. It demonstrates significant inhibitory activity against firefly luciferase, with an IC50 value of less than 0.1 μM. This compound is ideal for research applications focused on understanding the roles of YAP/TAZ in cancer biology and cellular signaling pathways.

GNE-7883 is a pan-TEAD inhibitor that disrupts the interaction between YAP/TAZ and TEAD transcription factors. This compound reduces chromatin accessibility at TEAD-binding sites and inhibits cell proliferation across various cell line models, demonstrating significant anti-tumor effects in vivo. Additionally, GNE-7883 addresses both intrinsic and acquired resistance to KRAS G12C inhibitors in multiple preclinical settings by targeting YAP/TAZ activation, making it a valuable tool for cancer research.

Pipecolic acid is a metabolite of lysine that acts as a YAP-GPX4 signaling modulator. It exhibits antioxidant properties and has been shown to reduce retinal vascular tube formation while mitigating ferroptosis. This compound enhances voltage-sensitive Ca2+ channel currents and can induce neuronal apoptosis, making it a valuable tool for research on diabetic retinopathy. Its ability to cross the blood-brain barrier further supports its application in neurological studies.

MY-1076 is a selective inhibitor of the Yes-associated protein (YAP), which plays a critical role in various cellular processes, including cell proliferation and apoptosis. This compound promotes the degradation of YAP, leading to induced apoptosis in tumor cells. MY-1076 demonstrates potent antiproliferative effects against gastric and colorectal cancer cell lines, including MGC-803, SGC-7901, HCT-116, and KYSE450, with IC50 values of 0.019, 0.017, 0.020, and 0.044 μM, respectively. It is a valuable tool for researching YAP's role in cancer biology and potential therapeutic interventions.

YAP/TEAD-IN-2 is a potent inhibitor of the YAP/TEAD protein complex. It effectively reduces luciferase activity driven by YAP/TEAD in 293T cells, demonstrating its function as a reliable research tool. Additionally, YAP/TEAD-IN-2 exhibits significant anti-proliferative effects against human pleural mesothelioma NCI-H226 cells. This compound is relevant for research exploring diseases related to dysregulation of the Hippo signaling pathway, particularly in the context of various cancer types.

K-975 is a selective and orally bioavailable TEAD inhibitor that disrupts protein-protein interactions between YAP1/TAZ and TEAD. This compound forms a covalent bond with Cys359 within the palmitate-binding pocket of TEAD through its acrylamide structure. K-975 demonstrates significant antitumor activity, particularly in the treatment of malignant pleural mesothelioma, making it a valuable tool for cancer research and therapeutic investigations targeting the YAP1/TAZ-TEAD signaling pathway.

VT104 is a potent and orally active inhibitor of the YAP/TAZ signaling pathway. It effectively prevents the palmitoylation of endogenous TEAD1 and TEAD3 proteins, thereby modulating downstream gene expression. This compound is valuable for research applications focused on cancer biology, particularly in studies aimed at understanding the role of YAP/TAZ in oncogenesis and tumor progression.

TED-347 is a potent irreversible allosteric inhibitor of the YAP-TEAD protein-protein interaction, exhibiting an EC50 of 5.9 μM for the TEAD4-Yap1 complex. The compound covalently binds to Cys-367 within the central pocket of TEAD4, with a Ki value of 10.3 μM. By inhibiting TEAD transcriptional activity, TED-347 demonstrates significant antitumor potential, making it a valuable tool for cancer research and therapeutic studies focused on the Hippo signaling pathway.

TT-10 is a potent activator of the YES-associated protein (YAP) and transcriptional enhancer factor domain (TEAD) signaling pathway. This compound enhances YAP-TEAD activity, which is crucial in regulating cell proliferation and survival. TT-10 is particularly useful for investigating heart diseases associated with cardiomyocyte loss, providing potential insights into therapeutic strategies for cardiac regeneration.

SWTX-143 is an orally active inhibitor of the YAP/TAZ-TEAD signaling pathway, targeting the palmitoylation pocket across all four TEAD isoforms. This compound demonstrates irreversible and selective suppression of YAP/TAZ-TEAD transcriptional activity, highlighting its potential in antitumor research. SWTX-143 serves as a valuable tool for investigating the mechanistic roles of YAP/TAZ-TEAD in oncogenesis and therapeutic strategies against cancer.

Super-TDU is a selective YAP antagonist that disrupts the YAP-TEAD interaction. This compound has demonstrated the ability to inhibit tumor growth in gastric cancer mouse models, making it a valuable tool for research in cancer biology and therapeutic development targeting the hippo signaling pathway. Its application in studying YAP-related signaling pathways offers insights into potential treatments for various malignancies.

YAP/TAZ Inhibitor-2 is a potent and orally bioactive compound that targets the TEAD-YAP/TAZ signaling pathway, demonstrating an EC50 of 3 nM. This inhibitor exhibits significant anti-proliferative effects, making it a valuable tool for research into tumorigenesis and cancer biology. Its antitumor activity further supports its application in studies focused on cellular proliferation and tumor growth regulation.

MSC-4106 is a potent, orally active inhibitor targeting the YAP/TAZ-TEAD signaling pathway. This compound effectively inhibits the auto-palmitoylation of TEAD1 and TEAD3, demonstrating significant biological activity. MSC-4106 has been shown to exert inhibitory effects in the NCI-H226 tumor xenograft model, making it a valuable tool for cancer research and therapeutic development.

YAP-TEAD-IN-2 is a potent inhibitor of the YAP-TEAD protein-protein interaction, exhibiting an IC50 value of 2.7 nM. This compound selectively interferes with the binding affinity between YAP and TEAD, thereby modulating the Hippo signaling pathway. YAP-TEAD-IN-2 is useful in various research applications, particularly in studies of cancer biology and cellular growth regulation, where the dysregulation of this interaction is implicated.

YTP-17 is a potent inhibitor of the YAP-TEAD protein-protein interaction, exhibiting an IC50 of 4 nM. This compound demonstrates significant anti-tumor activity, making it a valuable tool for cancer research. YTP-17 can be utilized to investigate the role of the YAP-TEAD pathway in various tumorigenic processes.

VS3 is a selective inhibitor of the YAP-TEAD interaction, effectively disrupting their binding by targeting TEAD4 Interface 3 with a dissociation constant (Kd) of 6 μM. This compound demonstrates significant anti-proliferative effects in various cancer cell lines, including HT29, HCT116, and A2780. VS3 is a valuable tool for investigating signaling pathways in colorectal adenocarcinoma and ovarian cancer research.

YAP/TAZ-TEAD-IN-3 is a potent inhibitor of the YAP/TAZ-TEAD protein-protein interaction, exhibiting an IC50 of 1.8 nM. This compound serves as a valuable tool for studies involving the Hippo signaling pathway and can be utilized in the development of PROTACs targeting TEAD1, such as PROTAC TEAD degrader-2. Its application extends to cellular and molecular research focused on cancer biology and tissue development regulation.

Hapalindole Q is a selective YAP1 inhibitor that functions by inducing the degradation of the Hippo pathway transcription factor YAP1 through the chaperone-mediated autophagy (CMA) pathway. With a dissociation constant (Kd) of 9.13 μM, Hapalindole Q effectively hinders Rab7-mediated autophagosome and lysosome fusion, resulting in a decrease in overall autophagy levels while preserving lysosomal function. This compound is relevant for cancer research, particularly in the context of liver and breast cancer investigations.

Hirudin (54-65) is a potent thrombin antagonist and YAP inhibitor that exhibits anticoagulatory properties. By blocking the anion binding site of thrombin, it inhibits both soluble and thrombus-bound thrombin, subsequently reducing YAP expression, nuclear translocation, and downstream signaling in vascular endothelial cells. This compound is employed in research related to liver obstructive cholestasis and liver fibrosis, as it ameliorates fibrosis symptoms, attenuates angiogenesis, and decreases inflammation and tissue hypoxia. Furthermore, Hirudin (54-65) promotes extracellular calcium influx in vascular smooth muscle, facilitating endothelium-independent contraction.