YAP

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.

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).

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

PY-60 can effectively activate YAP transcriptional activity against annexin A2 (ANXA2) (Kd value of 1.4 µM). PY-60 activates a pro-proliferative, YAP-dependent transcriptional program in adult animals that are able to remodel the epidermis through proliferation.

AICAR (Acadesine) is an AMPK activator that causes ZMP accumulation, thereby mimicking the stimulatory effect of AMP on both AMPK and AMPKK. It is commonly used in research related to diabetes, cardiovascular diseases, and tumors.

Lats-IN-1 is a potent and ATP-competitive Lats1 and Lats2 kinases inhibitor. It promotes Yap-dependent proliferation in postmitotic mammalian tissues.

LM-41 is a TEAD-binding agent with potential anticancer activity that strongly reduces the expression of CTGF, Cyr61, Axl and NF2, and can be used in the study of breast cancer.

IK-930 is an orally active TEAD inhibitor (EC50 < 0.1 µM) with potent potency.

MSC-4106, an orally active and potent YAP TAZ-TEAD inhibitor, disrupts TEAD1 and TEAD3 auto-palmitoylation and demonstrates significant efficacy in the NCI-H226 tumor xenograft model [1].

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

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.

TT-10 (TAZ-K), an activator of YES-associated protein (YAP)-transcriptional enhancer factor domain (TEAD) activity, has potential application in heart disease research, specifically for conditions characterized by loss of cardiomyocytes.

ML-7 hydrochloride (ML-7 HCl) is a cell-permeable, reversible, effective, ATP-competitive, and specific inhibitor of myosin light chain kinase (Ki: 300 nM); also inhibits smooth-muscle myosin light chain kinase, PKA, and PKC.

VT103 is an orally active and selective inhibitor of TEAD1 protein palmitoylation and is an analog of VT101. VT103 has potential antitumor activity by inhibiting YAP TAZ-TEAD-promoted gene transcriptionment, blocking TEAD auto-palmitoylation, and blocking the interaction between YAP TAZ and TEAD.VT103 can be used in the study of HER2-positive breast cancer, prostate cancer, and triple-negative breast cancer.

TED-347 is an irreversible and covalent inhibitor of TEAD4-Yap1 protein-protein interaction(EC50 of 5.9 μM), and inhibits glioblastoma cell viability.

YAP TAZ inhibitor-1 is a YAP TAZ inhibitor (IC50 <0.100 μΜ) for the study of abnormal immune function and cancer.

NIBR-LTSi is a selective LATS kinase inhibitor that also activates YAP signaling, promotes tissue stem cell expansion and tissue regeneration both in vitro and in vivo, accelerates liver regeneration in a mouse partial hepatectomy model, and is capable of expanding organoids derived from several mouse and human tissues.

YAP TAZ inhibitor-2 is a potent, orally active TEAD-YAP TAZ inhibitor with an EC50 value of 3 nM, demonstrating anti-proliferative and antitumor activity [1].

AICAR phosphate (Acadesine phosphate) is an AMPK activator and inhibitor of autophagy, YAP, and mitophagy. It serves as an adenosine analog, regulating glucose and lipid metabolism, and inhibiting the production of pro-inflammatory cytokines and iNOS.

MY-1076 is a potent YAP inhibitor with antigastric cancer activity.MY-1076 dose-dependently induced G2 M phase block, induced YAP degradation and apoptosis, and inhibited microtubule protein polymerization.MY-1076 inhibited the proliferation of MGC-803, SGC-7901, HCT-116, and KYSE450 cells.

MYF-01-37 (1-[3-Methyl-3-[3-(trifluoromethyl)anilino]pyrrolidin-1-yl]prop-2-en-1-one) is a novel covalent TEAD inhibitor.

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

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

KHKI-01215 is an effective NUAK2 inhibitor with anticancer activity, inhibiting the proliferation of SW480 cancer cells and inducing apoptosis in SW480 cells. KHKI-01215 is used for cancer research.

HC-258 is a direct TEAD inhibitor that forms a covalent bond with Cys380, a cysteine residue of TEAD proteins, and reduces the transcriptional levels and inhibits the migration of CTGF, CYR61, AXL and NF2 in MDA-MB-231 cells.

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-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.

MSC-5046 is a selective inhibitor of TEAD1.

YAP TAZ Inhibitor-4 (Compound 45) acts as an inhibitor of YAP TAZ, exhibiting inhibitory activity on TEAD transcriptional activation by preventing the interaction between YAP or TAZ and TEAD.

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.

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].

AF-2112, a TEAD inhibitor derived from Flufenamic acid, significantly diminishes the expression of CTGF, Cyr61, Axl, and NF2.

PROTAC YAP degrader-1, a targeted proteolysis promoting chimeric molecule, both degrades the YAP protein and inhibits its nuclear localization. This compound is formulated with Demethyl-NSC682769 as the target protein ligand, and utilizes (R,S,R)-AHPC-PEG2-C2-boc, which is the E3 ubiquitin ligase ligand + Linker conjugate. The linker incorporated in the design is Acid-PEG2-C2-Boc.

CV-4-26 (Compound 22) acts as a covalent inhibitor of TEAD. By inhibiting YAP TEAD-driven transcription, it diminishes the expression of CTGF and CYR61. Furthermore, CV-4-26 impedes colony formation in Huh7 and HepG2 cells, inducing cell cycle arrest and apoptosis (apoptosis). This compound demonstrates anti-tumoral activity against hepatocellular carcinoma (HCC) and hepatoblastoma (HB).

MSC-1254 is a reversible, selective, and covalent inhibitor of TEAD1, primarily utilized in cancer research.

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.

SWTX-143, a novel covalent inhibitor, specifically and irreversibly binds to the palmitoylation pocket of all four TEAD isoforms, inhibiting the transcriptional activity of the YAP TAZ-TEAD complex and demonstrating antitumor activity [1].