TEAD Inhibitor

MYF-03-69 (TEAD-IN-3) is a covalent and irreversible TEAD inhibitor with IC₅₀s of 385, 143, 558 and 173 nM for TEAD1, TEAD2, TEAD3 and TEAD4. MYF-03-69 disrupts YAP-TEAD association, suppresses TEAD transcriptional activity (IC₅₀ = 56 nM) and up-regulates apoptosis gene BMF. MYF-03-69 selectively inhibits mesothelioma cancer cells with defective Hippo signaling. MYF-03-69 can be used for the study of malignant pleural mesothelioma (MPM).

TEAD-IN-1 (Compound 2) is potent TEAD autopalmitoylation inhibitor, with an IC₅₀ of 603 nM. TEAD-IN-1 increases the interaction of TEAD and VGLL4. TEAD-IN-1 decreases the interaction of YAP and TEAD. TEAD-IN-1 can be used for the research of cancer.

OPN-9652 is a potent, orally active, and covalent TEAD inhibitor (MSTO-211H TEAD IC₅₀ = 0.005 µM) targeting the central palmitate binding pocket of TEADs. OPN-9652 reduces TEAD-dependent reporter activity and expression of TEAD targets (CTGF and CYR61). OPN-9652 resensitizes drug-tolerant SOX10 KO cells to BRAFi + MAPKi. OPN-9652 delays the onset of tumor resistance to BRAFi + MEKi from minimal residual disease (MRD) in a BRAF mutant A375 xenograft mouse model. OPN-9652 can be used for melanoma research.

M3686 (Compound 29) is a potent, selective TEAD1 inhibitor with an IC₅₀ value of 51 nM. M3686 also shows weaker binding activity on TEAD3. M3686 potently inhibits cell viability against YAP-dependent NCI-H226 cell line with an IC₅₀ value of 0.06 uM. M3686 shows strong anti-tumor effects in the NCI-H226 xenograft model.

TEAD-IN-21 is a potent and orally active pan-TEAD inhibitor with an IC₅₀ of 3 nM. TEAD-IN-21 effectively inhibited the proliferation of Huh-7 cells. TEAD-IN-21 selectively downregulates TEAD-dependent downstream genes. TEAD-IN-21 achieves tumor regression in a liver cancer-derived tumor xenograft mice model. TEAD-IN-21 can be used in the research of hepatocellular carcinoma (HCC).

LC-TEAD01 is a potent covalent transcription enhancer-associated domain (TEAD) inhibitor with an IC₅₀ of 116 nM and a K_i of 0.132 μM. LC-TEAD01 disrupts the TEAD-YAP interaction and inhibits TEAD-dependent transcriptional activity. LC-TEAD01 suppresses the proliferation of NF2-deficient cancer cells. LC-TEAD01 inhibits tumor growth in NF2-deficient xenograft models. LC-TEAD01 can be used in studies related to NF2-deficient malignant pleural mesothelioma.

OPN-9643 is a covalent inhibitor targeting the central palmitate binding pocket of TEADs with an IC₅₀ of 15 nM, preventing autopalmitoylation and reducing TEAD-driven luciferase activity and canonical TEAD targets, CTGF and CYR61. OPN-9643 can be used for the research of cancer, such as melanoma.

EA-C15 is a potent and selective TEAD inhibitor with an IC₅₀ of 0.34 μM. EA-C15 covalently binds to the TEAD palmitoylation site, blocks palmitoylation and transcriptional activity, and inhibits YAP-dependent cancer cell proliferation and YAP-TEAD target gene (CTGF and CYR61) transcription. EA-C15 can be used for cancer research.

VT102 is a TEAD1 inhibitor with a human IC₅₀ of 391 nM. VT102 inhibits auto-palmitoylation, attenuates YAP/TEAD1 interaction, reduces expression of TEAD target genes, and inhibits YAP-mediated luciferase reporter activity. VT102 exerts weak cell growth inhibitory activity in cancer cells. VT102 can be used for the research of cancer.

TEAD-IN-23 (Compound 22) is an efficient pan-TEAD inhibitor with an IC₅₀ of 10 nM. TEAD-IN-23 exhibits potent anti-proliferative activity in both NCI-H226 and MSTO-211H. TEAD-IN-23 causes complete tumor regression in the MSTO-211H xenograft tumor model. TEAD-IN-23 can be used for the study of mesothelioma and hepatocellular carcinoma.

LC-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.

YAP/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).

pan-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 (AUC_0–∞ = 228.7 μg/mL·min, T_1/2 = 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.

VT101 is a TEAD inhibitor with an IC₅₀ of 454 nM. VT101 is applicable for cancer research.

DC-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.

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

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