hippo pathway

IHMT-MST1-58 is a STE20-like protein 1 kinase (MST1) inhibitor (IC50:23 nM) with high efficiency, selectivity and oral activity. IHMT-MST1-58 can be used to study type 1 or type 2 diabetes.

XMU-MP-1 is a reversible and selective MST1/2 kinase inhibitor, and its IC50 values for MST1 and MST2 are 71.1 nM and 38.1 nM, respectively.

Pim1/AKK1-IN-1 (LKB1/AAK1 dual inhibitor) is a potent multi-kinase inhibitor with Kd values of 35 nM/53 nM/75 nM/380 nM for Pim1/AKK1/MST2/LKB1 respectively, and also inhibits MPSK1 and TNIK.

Cerdulatinib hydrochloride (PRT2070 hydrochloride) is an oral active, multi-targeted tyrosine kinase inhibitor with IC50 of 12 nM/6 nM/8 nM/0.5 nM and 32 nM for JAK1/JAK2/JAK3/TYK2 and Syk, respectively. Also inhibits 19 other tested kinases with IC50 less than 200 nM.

I3MT-3 (HMPSNE) (HMPSNE) is a potent, selective and cell membrane permeability inhibitor of 3-mercaptopyruvate sulfur transferase (3MST), which targets the persulfated cysteine residues located at the active site of 3MST.

EN171, a covalent ligand, selectively binds to C38 and C96 on 14-3-3, intensifying 14-3-3's interactions with ERα, YAP, and TAZ. This action impairs both estrogen receptor and Hippo pathway transcriptional activities. Beyond serving as a molecular glue to augment native protein interactions, EN171 also functions as a covalent recruiter for 14-3-3 in heterobifunctional molecules. This facilitates the sequestration of nuclear neo-substrates, such as BRD4 and BLC6, into the cytosol.

MY-1576 is a FAK inhibitor with an IC50 of 8 nM. It activates the Hippo pathway, thereby inhibiting YAP/TAZ regulation. Additionally, MY-1576 effectively suppresses tumor growth in the KYSE30 xenograft mouse model, demonstrates good safety, and efficiently downregulates FAK autophosphorylation and YAP/TAZ levels in vivo.

EMT inhibitor-1 is a compound that inhibits Hippo and Wnt signaling pathways, as well as TGF- macrophages (TGF-), exhibiting antitumor activity.

MR24 is a derivative of G-5555 and acts as an inhibitor of mammalian STE20-like (MST) kinases. It selectively targets MST3 and MST4, with EC50 values of 57 nM and 583 nM, respectively.

Tubulin polymerization-IN-79 (Compound C20) acts as an inhibitor of microtubule polymerization. It exhibits significant antiproliferative activity against esophageal cancer cells, such as KYSE450 (IC50=0.36 μM) and EC-109 (IC50=0.63 μM). In esophageal cancer cells, Tubulin polymerization-IN-79 occupies the colchicine binding site, disrupting the microtubule network's integrity, activating the Hippo signaling pathway, downregulating the oncogenic protein YAP, and inducing G2/M phase arrest and apoptosis. This compound shows promise for esophageal cancer research.

MST3-IN-1 is a selective and orally active MST3 inhibitor with an IC50 of 122.4 nM. It exhibits antiproliferative activity in HepG2 cells, effectively induces apoptosis, and causes cell cycle arrest at the G2/M phase. In HepG2 xenograft mouse models, MST3-IN-1 significantly suppresses tumor growth, making it useful for liver cancer research.

MST3-IN-1 TFA (Compound LD-1) is a selective and orally bioactive MST3 inhibitor with an IC50 value of 122.4 nM. It exhibits antiproliferative effects on HepG2 cells, effectively inducing apoptosis and arresting the cell cycle in the G2/M phase. Additionally, MST3-IN-1 TFA significantly suppresses tumor growth in a HepG2 xenograft mouse model, making it applicable for liver cancer research.

JA310 is a highly selective inhibitor of the MST3 kinase, demonstrating significant cellular potency with an EC50 value of 106 nM [1].

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-IN-1 (Compound (+)-1) is an autophagy inhibitor specifically targeting YAP1. It binds to the Hippo pathway transcription factor YAP1 with a Kd of 9.13 μM, promoting its degradation through the chaperone-mediated autophagy (CMA) pathway. This process inhibits the Rab7-mediated fusion of autophagosomes with lysosomes and decreases autophagy levels without affecting lysosomal function. YAP-IN-1 shows potential for cancer research, including in hepatocellular carcinoma and breast cancer.

TEAD1/3/4-IN-1 (compound 1) is an inhibitor of TEAD1/3/4 that suppresses YAP/TAZ-TEAD interactions. It exhibits antitumour activity against NF2-deficient NCI-H226 cells and may be employed in studies of cancer and diseases mediated by Hippo pathway abnormalities.

mCMY020 is a covalent TEAD inhibitor that effectively reduces YAP (Yes-associated protein)-driven transcription and selectively slows the proliferation of Hippo pathway-deficient cancer cells. It is applicable in cancer research.

VT02956 is an inhibitor of LATS with an IC50 of 0.76 nM for LATS1 and 0.52 nM for LATS2. It targets the Hippo signaling pathway and suppresses the growth of ER+ breast cancer cell lines and patient-derived tumor organoids, as well as the expression of ESR1.

YAP/TEAD-IN-2 (Compound T-1) is an inhibitor of YAP/TEAD. This compound suppresses luciferase activity driven by YAP/TEAD in 293T cells and exhibits strong antiproliferative effects on human pleural mesothelioma NCI-H226 cells. YAP/TEAD-IN-2 is applicable for studying diseases associated with disruptions in the Hippo pathway, particularly cancer.

MY-875 is a potent microtubulin polymerization inhibitor that competes at colchicine binding sites, exhibiting an IC50 value of 0.92 μM. It effectively suppresses microtubulin polymerization, exerting its inhibitory effect. Additionally, MY-875 exerts its biological impact by activating the Hippo pathway, inducing apoptosis, and displaying commendable anticancer activity [1].

VT02956 is a LATS inhibitor ( IC 50 : 0.76 nM for LATS1, 0.52 nM for LATS2). VT02956 targets the Hippo pathway. VT02956 inhibits ESR1 expression and growth of ER+ breast cancer cell lines and patient-derived tumor organoids .

TEAD-IN-11 (compound 38) exhibits potent inhibitory activity against TEAD1, TEAD2, and TEAD3, with IC50 values of 8.7, 3.4, and 5.6 nM, respectively. TEAD-IN-11 (compound 38) functions as a selective covalent inhibitor of these TEAD isoforms. TEAD-IN-11 (compound 38) is applicable to investigations involving Hippo pathway signaling, TEAD-mediated transcriptional regulation, and cancer-associated proliferative signaling mechanisms.

alpha-Ionone acts as an agonist for the olfactory receptor OR10A6. It induces apoptosis by activating OR10A6 and increasing the phosphorylation level of the LATS-YAP-TAZ signaling axis in the Hippo pathway, thereby inhibiting tumorigenesis and tumor progression in both in vitro and in vivo experiments.