TEAD
TEAD (TEA domain) transcription factors comprise a highly conserved family of DNA-binding proteins that function as the major transcriptional effectors of the Hippo signaling pathway and regulate cell growth, proliferation, tissue homeostasis, regeneration, and embryonic development[1][2]. Mechanistically, TEAD proteins bind genomic target sequences and cooperate with the transcriptional coactivators YAP and TAZ to control transcriptional programs that govern cellular proliferation, differentiation, and survival[1][3]. Through this YAP/TAZ-TEAD transcriptional module, Hippo pathway activity is translated into gene-expression outputs that influence developmental processes and organ homeostasis[1][4]. In disease contexts, increased TEAD transcriptional activity has been associated with tumorigenesis and therapeutic resistance, and dysregulated Hippo signaling can promote TEAD-dependent oncogenic transcription in multiple cancer types[3][5][6]. Experimental studies further demonstrate that disruption of YAP-TEAD interactions suppresses YAP-dependent gene expression and oncogenic transformation, supporting TEAD as a critical functional node in cancer biology[3]. Compared with related family members, TEAD1, TEAD3, and TEAD4 are broadly expressed in multiple adult tissues, whereas TEAD2 displays a more restricted embryonic expression pattern and is largely absent from adult tissues, indicating distinct biological roles despite strong structural conservation[7]. Research on TEAD-targeted therapeutics has therefore focused on inhibitors that disrupt TEAD-mediated transcriptional complexes or directly antagonize TEAD activity, providing valuable experimental tools for investigating Hippo pathway function and evaluating anticancer strategies[5][8][2].
References:
- [1]. Lin KC, et al. Regulation of the Hippo Pathway Transcription Factor TEAD. Trends Biochem Sci. 2017 Nov;42(11):862-872. [Content Brief]
- [2]. Chapeau EA, et al. Direct and selective pharmacological disruption of the YAP-TEAD interface by IAG933 inhibits Hippo-dependent and RAS-MAPK-altered cancers. Nat Cancer. 2024 Jul;5(7):1102-1120. [Content Brief]
- [3]. Zhou Y, et al. The TEAD Family and Its Oncogenic Role in Promoting Tumorigenesis. Int J Mol Sci. 2016 Jan 21;17(1):138. [Content Brief]
- [4]. Currey L. TEAD family transcription factors in development and disease. Development. 2021 Jun 15;148(12):dev196675. [Content Brief]
- [5]. Holden JK, et al. Targeting the Hippo Pathway and Cancer through the TEAD Family of Transcription Factors. Cancers (Basel). 2018 Mar 20;10(3):81. [Content Brief]
- [6]. Cunningham R. The Hippo pathway in cancer: YAP/TAZ and TEAD as therapeutic targets in cancer. Clin Sci (Lond). 2022 Feb 11;136(3):197-222. [Content Brief]
- [7]. Landin-Malt A, et al. An evolutionary, structural and functional overview of the mammalian TEAD1 and TEAD2 transcription factors. Gene. 2016 Oct 10;591(1):292-303. [Content Brief]
- [8]. Gibault F, et al. Targeting Transcriptional Enhanced Associate Domains (TEADs). J Med Chem. 2018 Jun 28;61(12):5057-5072. [Content Brief]
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TEAD Related Products (38)
Related Products (38)
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TEAD degrader-1
0 ImagesCat. No.: HY-184179CAS No.: 3103984-17-1TEAD degrader-1 is a potent FBXO22-mediated molecular glue degrader of TEAD, with a 24 h DC50 of 1.0 nM. TEAD degrader-1 binds reversibly and covalently to FBXO22 C326, assembles a functional ternary complex, and mediates proteasomal degradation of TEAD. TEAD degrader-1 exhibits high selectivity for the Hippo pathway and specifically downregulates only TEAD and its downstream target proteins. TEAD degrader-1 is applicable to research related to malignant pleural mesothelioma and non-small cell lung cancer.
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TEAD ligand-Linker Conjugate 1
0 ImagesCat. No.: HY-186023CAS No.: 2918762-34-0
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TEAD ligand 6
0 ImagesCat. No.: HY-186118TEAD ligand 6 is a TEAD ligand. TEAD ligand 6 serves as a ligand for target protein for PROTAC (Ligands for Target Protein for PROTAC) and is used to develop and design PROTAC-based TEAD degraders, such as KG-FP-003 (HY-186117). TEAD ligand 6 applies to glioblastoma research.
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GNE-2181
0 ImagesCat. No.: HY-187181CAS No.: 2933893-78-6GNE-2181 is an orally active, blood-brain barrier-penetrant pan-TEAD transcription factor inhibitor, with IC50 values of 13, 26, 61 and 17 nM against TEAD1, TEAD2, TEAD3 and TEAD4, respectively. GNE-8021 allosterically disrupts the TEAD-YAP/TAZ interaction and inhibits TEAD-mediated oncogenic transcriptional programs via the Hippo signaling pathway. GNE-8021 suppresses YAP-driven tumor cell growth. GNE-2181 inhibits the growth of intracranial tumor models in vivo. GNE-2181 can be used for research on brain metastasis of lung cancer.
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PROTAC TEAD degrader-2
0 ImagesCat. No.: HY-186021CAS No.: 2918762-17-9PROTAC TEAD degrader-2 (Compound 31) is an efficient TEAD1 PROTAC degrader with a DC50 of 0.6 nM. PROTAC TEAD degrader-2 inhibits the YAP/TAZ-TEAD interaction, with a IC50 of 1.8 nM. PROTAC TEAD degrader-2 exhibits significant selective inhibitory activity against YAP-dependent cancer cells and effectively suppresses the transcriptional activity mediated by YAP. PROTAC TEAD degrader-2 can be used for research on mesothelioma and glioma.
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LC-TD-05
0 ImagesCat. No.: HY-183753LC-TD-05 is a non-covalent inhibitor of TEAD1, TEAD2 and TEAD4, with IC50 values of 116.6 nM, 168.7 nM and 68.3 nM, respectively; it shows weak activity against TEAD3, with a human IC50 of 1261.0 nM. LC-TD-05 induces apoptosis in hepatocellular carcinoma cells. LC-TD-05 can be used for the research of hepatocellular carcinoma.
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YAP/TAZ-TEAD-IN-3
0 ImagesCat. No.: HY-186022CAS No.: 2714434-41-8YAP/TAZ-TEAD-IN-3 is a YAP/TAZ-TEAD interaction inhibitor with an IC50 of 1.8 nM. YAP/TAZ-TEAD-IN-3 can be used as a TEAD1 ligand to construct PROTACs, such as PROTAC TEAD degrader-2 (HY-186021).
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pan-TEAD-IN-1
0 ImagesCat. No.: HY-159912CAS No.: 3027484-09-6pan-TEAD-IN-1 (Compound 3) is an orally active pan-TEAD inhibitor targeting the palmitoylation site of TEAD, disrupting its interaction with the coactivators YAP/TAZ, thereby suppressing the transcriptional upregulation of oncogenes (e.g., Ctgf and Cyr61) in the Hippo signaling pathway. pan-TEAD-IN-1 exhibits excellent activity with a luciferase IC50 of 0.36 nM and an H226 cell IC50 of 1.52 nM. It also shows favorable pharmacokinetics (AUC0–∞ = 228.7 μg/mL·min, T1/2 = 183.9 min). In TEAD-dependent xenograft mouse models, pan-TEAD-IN-1 significantly inhibited tumor growth, showing promise for research in TEAD-dependent cancers.
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VT101
0 ImagesCat. No.: HY-182672CAS No.: 65194-64-1
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DC-TEAD3in03
0 ImagesCat. No.: HY-147209DC-TEAD3in03 is a subtype-selective and covalent TEAD3 inhibitor with an IC50 of 0.16 μM. DC-TEAD3in03 exhibits the inhibitory activity on TEAD1/2/4 reduced by more than 100 times. DC-TEAD3in03 has the IC50 for TEAD3 of 1.15 μM in the GAL4-TEAD reporter gene experiment in cells, and it does not interfere with the β-catenin pathway. DC-TEAD3in03 reduces the growth rate of the zebrafish tail fin. DC-TEAD3in03 can be used to study the proportional growth of appendages in vertebrates.
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PROTAC TEAD/IAP degrader-1
0 ImagesCat. No.: HY-181594PROTAC TEAD/IAP degrader-1 is a TEAD/IAP PROTAC degrader. PROTAC TEAD/IAP degrader-1 is also a specific and Nongenetic inhibitor of apoptosis protein (IAP)-dependent protein eraser (SNIPERs). PROTAC TEAD/IAP degrader-1 recruits cIAP1 to form ternary complexes, induces ubiquitination, proteasomal TEAD1, TEAD4 degradation. PROTAC TEAD/IAP degrader-1 inhibits TEAD transcriptional activity, reduces CTGF expression, and reduces cell proliferation. PROTAC TEAD/IAP degrader-1 can be used for the research of mesothelioma.
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PROTAC TEAD1/IAP degrader-2
0 ImagesCat. No.: HY-181537PROTAC TEAD1/IAP degrader-2 is an IAP-harnessing TEAD1 PROTAC degrader, with a DC50 of 170 nM against TEAD1 in NCI-H2052 cells. PROTAC TEAD1/IAP degrader-2 exhibits moderate antiproliferative activity in Hippo pathway-dependent mesothelioma cells. PROTAC TEAD1/IAP degrader-2 inhibits the expression of CTGF, but with a weaker effect than the TEAD inhibitor VT-107 (HY-134957). PROTAC TEAD1/IAP degrader-2 can be used in mesothelioma-related research.
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TEAD-IN-24
0 ImagesCat. No.: HY-180514CAS No.: 3034813-75-4TEAD-IN-24 (Example 65) is a TEAD inhibitor. TEAD-IN-24 exhibits anti-cancer activity against non-small cell lung cancer.
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TEAD ligand-Linker Conjugate 3
0 ImagesCat. No.: HY-181607TEAD ligand-Linker Conjugate 3 (the blue structure + black structure of A536 in the literature) is a conjugate of a TEAD1-targeting ligand and a linker. TEAD ligand-Linker Conjugate 3 can be coupled with an IAP ligand (HY-181531) to form an IAP-recruiting bifunctional protein degrader (IPD) (HY-181594), also known as a SNIPER degrader. This TEAD SNIPER simultaneously binds to the TEAD1 palmitoylation pocket and the BIR3 domain of cIAP1 to form a ternary complex, efficiently inducing the ubiquitination and degradation of both TEAD1 and cIAP1 (DC50=110 nM, Dmax=51%; IC50=122 nM for cIAP1). TEAD ligand-Linker Conjugate 3 and its synthesized SENIPER molecule can be utilized in research on Hippo pathway dysregulation-related diseases, such as NF2-mutant tumors.
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TEAD ligand 3
0 ImagesCat. No.: HY-181538TEAD ligand 3 (compound S20) is a TEAD ligand. As a target protein ligand, TEAD ligand 3 can be used in the synthesis of PROTAC TEAD1/IAP degrader-2 (HY-181537).
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