emt inhibitor-1

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

Leptomycin B (LMB) is a potent inhibitor of the nuclear export of proteins and is a potent antifungal antibiotic blocking the eukaryotic cell cycle. Leptomycin B inactivates CRM1 exportin 1 by covalent modification at a cysteine residue.

JNK-1-IN-4 (Compound E1) is an inhibitor of JNK, targeting JNK-1, JNK-2, and JNK-3 with IC50 values of 2.7, 19.0, and 9.0 nM, respectively. This compound inhibits the phosphorylation of c-Jun and reduces the expression of TGF-β1-induced EMT markers (such as fibronectin and α-SMA). JNK-1-IN-4 exhibits favorable pharmacokinetic properties with a bioavailability of 69%. Additionally, it demonstrates antifibrotic effects in a Bleomycin-induced mouse model of idiopathic pulmonary fibrosis.

AXL Angiokinase-IN-1 (compound 11b) is an inhibitor of AXL triple angiokinase, with an IC50 of 3.75 nM for AXL expression. This compound suppresses epithelial-mesenchymal transition (EMT) in Bxpc-3 cells and prevents metastasis in lung cancer cells. Additionally, AXL Angiokinase-IN-1 impairs the functions of vascular and fibroblast cells and induces apoptosis in both cancer and fibroblast cells. It is characterized by low toxicity and favorable metabolic stability.

FGFRs-IN-1 (Compound A16) is an orally active inhibitor targeting FGFR1 2 3 4, with IC50 values of 2.3, 7, 11, and 163 nM respectively. It also inhibits VEGFR1 2 3, Abl, and Flt3, with IC50 values of 61, 176, 112, 26, and 353 nM. The compound shows weak inhibition of CYP enzymes. FGFRs-IN-1 reduces the expression of α-SMA and collagen I, and it inhibits epithelial-mesenchymal transition (EMT) in A549 cells stimulated by TGF-β1. Additionally, FGFRs-IN-1 demonstrates anti-inflammatory activity in mouse models of lung fibrosis induced by Bleomycin and liver fibrosis induced by CCl4.

S118 is an orally active inhibitor of the sphingosine-1-phosphate receptor 2 (S1P2 receptor). It prevents the binding of the S1P2 receptor to dapper1 (Dpr1), reduces the accumulation of β-catenin, and blocks the nuclear translocation of the S1P2 receptor. This process inhibits inflammation, fibrosis, and epithelial-mesenchymal transition (EMT), thereby exhibiting anti-idiopathic pulmonary fibrosis (IPF) activity. S118 is considered promising for research in idiopathic pulmonary fibrosis.

HDAC/PSMD14-IN-1 is a derivative of gambogic acid. It serves as an orally active dual inhibitor targeting PSMD14 and HDAC1, with IC50 values of 238.7 nM and 141.2 nM, respectively. The compound exhibits significant cytotoxicity against ESCC cell lines (IC50: 30-250 nM) and effectively reverses epithelial-mesenchymal transition (EMT). Additionally, HDAC/PSMD14-IN-1 can induce apoptosis. In KYSE30 cell xenograft models in mice, it displays antitumor activity. HDAC/PSMD14-IN-1 is useful for researching esophageal cancer treatment.

CYP1B1-IN-3 is a potent, selective inhibitor of CYP1B1, exhibiting IC50 values of 6.6 nM for CYP1B1, 347.3 nM for CYP1A1, and >10000 nM for CYP1A2. It also impedes cell migration and invasion, and inhibits the P-gp, AKT ERK, FAK SRC, and EMT pathways [1].

CPUL1, a TrxR inhibitor, exhibits proliferation-inhibitory and anti-metastatic effects on A549 cells by modulating epithelial-mesenchymal transition (EMT) through the induction of ROS-mediated ERK JNK signaling, achieved by inhibiting TrxR1 enzyme activity. The efficacy of CPUL1 is enhanced when used in conjunction with α-Lipoic Acid or Dithiodipropionic acid [1].

DT-6, a potent TGF-β1 inhibitor, impedes M2 macrophage-induced epithelial-to-mesenchymal transition and the invasive migration of cancer cells, thereby showing potential for cancer research applications [1].

Bisabosqual A is a potent asparagine synthetase (ASNS) inhibitor with an IC 50 of 10.7 μM, capable of covalently modifying the K556 site of the ASNS protein. It induces oxidative stress and apoptosis, while inhibiting autophagy, cell migration, and epithelial-mesenchymal transition (EMT), thereby slowing cancer cell development [1].