epithelial cancer

Valspodar (PSC 833), a specific P-glycoprotein inhibitor and MDR regulator, is commonly used as a chemical sensitizer in the study of advanced epithelial ovarian cancer.

AXL-IN-13 is a potent and orally active AXL inhibitor with an IC50 of 1.6 nM and a Kd of 0.26 nM. It exhibits anticancer activity, reverses TGF-β1-induced epithelial-mesenchymal transition (EMT), and inhibits cancer cell migration and invasion.

Sulindac (Sulindac sulfoxide) is a sulfinylindene derivative prodrug with potential antineoplastic activity. Converted in vivo to an active metabolite, sulindac, a nonsteroidal anti-inflammatory drug (NSAID), blocks cyclic guanosine monophosphate-phosphodiesterase (cGMP-PDE), an enzyme that inhibits the normal apoptosis signal pathway; this inhibition permits the apoptotic signal pathway to proceed unopposed, resulting in apoptotic cell death.

Dextran sulfate sodium salt (MW 36,000–50,000) is a medium molecular weight polyanionic dextran derivative with strong intestinal epithelial permeability. It is the most commonly used agent for inducing inflammatory bowel disease (IBD) models, effectively inducing both acute and chronic colitis. Its mechanism may involve macrophage dysfunction and gut microbiota dysbiosis. Due to its colonic epithelial toxicity, long-term use can also induce colorectal cancer models.

Allicin exerts antioxidant, bactericidal, anti-cancer, anti-inflammatory activities, it exerts an inhibitory immunomodulatory effect on intestinal epithelial cells. Allicin could significantly inhibit vascular smooth muscle cells' proliferation and migration induced by insulin, which may be related to the inhibition of the activation of ERK signal path. Allicin is beneficial in reducing blood cholesterol, triglycerides levels and systolic blood pressure in hypercholesterolemic rats, it may beneficially affect two risk factors for atherosclerosis-hyperlipidemia and hypertension.

1. Berberine (Umbellatine) is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism. 2. Berberine may as a broad-spectrum anti-microbial medicine, a complementary therapeutic agent for HIV/AIDS. 3. Berberine seems to act as an herbal antidepressant and a neuroprotector against neurodegenerative disorders. 4. Berberine is used in histology for staining heparin in mast cells. As a natural dye, berberine has a colour index of 7516. 5. Berberine reduces hepatic fat content in rats with nonalcoholic fatty liver disease; also prevents proliferation of hepatic stellate cells (HSCs), which are central for the development of fibrosis during liver injury. 6. Berberine can ameliorate proinflammatory cytokines-induced intestinal epithelial tight junction damage in vitro, and berberine may be one of the targeted therapeutic agents that can restore barrier function in intestinal disease states. 7. Berberine has antineoplastic effects, including breast cancer, leukemia, melanoma, epidermoid carcinoma, hepatoma, pancreatic cancer, oral carcinoma, tongue carcinoma, glioblastoma, prostate carcinoma and gastric carcinoma, etc.

T-1840383 is an inhibitor of VEGF-induced VEGFR-2 phosphorylation and HGF-induced c-Met phosphorylation in vascular endothelial cells and cancer epithelial cells.

KY-05009 is a chemical compound that effectively suppresses TGF-β1-induced epithelial-to-mesenchymal transition (EMT) in human lung adenocarcinoma cells, reduces TNIK protein expression and the transcriptional activity of Wnt target genes, and promotes apoptosis in cancer cells, displaying anti-cancer properties. Furthermore, it functions as an ATP-competitive Traf2- and Nck-interacting kinase (TNIK) inhibitor with a Ki of 100 nM.

LG100268 is a potent, selective, and orally active retinoid X receptor (RXR) agonist that agonizes RXR-α, RXR-β, and RXR-γ at the nanomolar level, selectively exceeding the RAR by three orders of magnitude.LG100268 is capable of inducing transcriptional activation in adipocytes; affecting the RXRs and their chaperone receptor, Foxl2 Dmrt1, to induce flounder masculinization in juvenile flounder; inhibits keratin 17 expression in nigrostriatal epithelial cells; and increases PD-L1 expression in HER2 or triple-negative breast cancer.

Ciglitazone (ADD 3878) is a potent and selective PPARγ agonist (EC50: 3 μM) and oral hypoglycemic agent. Ciglitazone inhibits proliferation and differentiation of th17 cells, decreases insulin levels, vascular endothelial growth factor production and blood pressure, and induces cell cycle arrest in gastric cancer cells. Selegiline induces apoptosis in opossum kidney epithelial cells and activates nuclear translocation of p38 MAPK and apoptosis-inducing factor (AIF). Ciglitazone exhibits hypoglycaemic activity in animal models of obesity and hyperglycaemia.

HJ445A is a highly efficient and selective MYOF inhibitor with excellent water solubility, utilized for the treatment of gastric cancer. In gastric cancer cells MGC803 and MKN45, HJ445A exhibits significant antiproliferative properties with IC50 values of 0.16 μM and 0.14 μM, respectively. The compound binds to the MYOF-C2D domain with a KD value of 0.17 μM and hinders the migration of gastric cancer cells by reversing the epithelial-mesenchymal transition (EMT) process. It also inhibits colony formation in MKN45 cells in a concentration-dependent manner. Remarkably, compared to compound 6y, HJ445A's water solubility is improved by approximately 170 times. Moreover, HJ445A demonstrates superior antitumor effects in vivo.

Pixatimod (also known as PG-545) is a synthetic carbohydrate-modified heparan sulfate mimetic and a Toll-like receptor 9 (TLR9) agonist. It exhibits potential immunostimulatory, antitumor, and antiviral effects. Pixatimod effectively inhibits SARS-CoV-2 by disrupting the spike protein-ACE2 interaction. Additionally, it blocks various cancer-promoting processes such as cell proliferation, invasion, metastasis, angiogenesis, and epithelial-mesenchymal transition. These effects have demonstrated significant efficacy in numerous mouse cancer models, including about 30 xenograft models and 20 syngeneic models. Pixatimod has been tested in combination with several approved anticancer compounds, showing clinical potential when used with gemcitabine, paclitaxel, sorafenib, platinum compounds, and anti-PD-1 antibodies.

Pixatimod (also known as PG-545) is a synthetic modified heparan sulfate mimetic and an agonist of Toll-like receptor 9 (TLR9), showcasing potential immunostimulatory, antitumor, and antiviral properties. It effectively inhibits SARS-CoV-2 by disrupting the interaction between the spike protein and ACE2. Moreover, Pixatimod blocks cancer-promoting processes such as cell proliferation, invasion, metastasis, angiogenesis, and epithelial-mesenchymal transition. These activities have demonstrated significant efficacy across various murine cancer models, including approximately 30 xenograft models and 20 syngeneic models. Pixatimod has been tested in combination with several approved anticancer compounds, underscoring its clinical potential, with drugs like gemcitabine, paclitaxel, sorafenib, platinum-based compounds, and an anti-PD-1 antibody.

Uridine triphosphate (UTP) is a purine nucleotide P2U receptor agonist with potential use in lung cancer treatment. By activating P2Y2 receptors, it enhances the proliferation of human cancerous ductal epithelial cells. Additionally, UTP induces fibrotic responses in cardiac fibroblasts through P2Y2 receptor activation and prolongs the action potential duration of guinea pig papillary muscles via the P2Y2 purinergic receptor.

RNAse L RIBOTAC (compound C64) is an RNA-degrading chimera that binds to a four-way RNA helix called SL5 located in the 5’ UTR of the SARS-CoV-2 RNA genome, thereby inhibiting viral replication in pulmonary epithelial cancer cells.

EMT inhibitor-3 (compound 11i) is an epithelial-mesenchymal transition (EMT) inhibitor that effectively suppresses the proliferation, migration, and invasion of SK-N-SH neuroblastoma cells, with an IC50 value of 2.5 μM. It induces mitochondrial-mediated intrinsic apoptosis in tumor cells by enhancing the Bax Bcl-2 protein expression ratio, promoting the release of cytochrome C from mitochondria, and activating caspase 9 and caspase 3. EMT inhibitor-3 is applicable for cancer research.

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.

LSD1-IN-39 (Compound 14) is a reversible inhibitor of LSD1 with an IC50 of 0.18 μM, showing broad-spectrum antiproliferative activity against cancer cells, inhibiting HepG2 cell migration, and suppressing epithelial-mesenchymal transition. Additionally, LSD1-IN-39 exhibits antitumor activity in mouse models.

Coprostanone (5β-cholestan-3-one) is an active metabolite of hydroxycholesterol and cholesterol. It induces apoptosis in primary gallbladder epithelial cells in dogs. Coprostanone holds potential for research into colon cancer or adenomatous polyps.

LA-CB1 is a derivative of Abemaciclib that targets CDK4/6 and promotes their degradation via the ubiquitin-proteasome pathway, thereby blocking the CDK4/6-Cyclin D1-Rb-E2F axis and inducing G0/G1 cell cycle arrest and apoptosis (Apoptosis). It demonstrates antiproliferative activity against MDA-MB-231 cells with an IC50 of 0.27 µM and effectively inhibits epithelial-mesenchymal transition, cell migration, invasion, and angiogenesis. In highly invasive models like triple-negative breast cancer (TNBC), LA-CB1 significantly suppresses tumor growth, showing robust dose-dependent antitumor activity. This compound can be utilized in breast cancer research.

Lyso-Monosialoganglioside GM3 (Lyso-GM3) is an analog of Ganglioside GM3 with antitumor properties. It inhibits the increase in EGFR kinase activity induced by EGF in A431 epithelial cancer cells.

Ran-IN-1 (Compound M36) is an orally active and selective inhibitor of Ran GTPase. It binds allosterically with high specificity to the switch II pocket of GDP-bound Ran (RanGDP), stabilizing its inactive state and reducing the formation of active Ran-GTP. Ran-IN-1 induces apoptosis in epithelial ovarian cancer (EOC) cells and inhibits DNA repair pathways such as homologous recombination (HR) and non-homologous end joining (NHEJ). This compound shows potential for research in epithelial ovarian cancer, particularly in high-grade serous carcinoma.

Anti-STEAP2 Antibody (AZD0516 antibody) is a selective inhibitor of the prostate-specific six transmembrane epithelial antigen 2 (STEAP2). It inhibits the proliferation, migration, and invasion of prostate cancer cells by blocking the STEAP2-mediated ERK/MAPK signaling pathway. Anti-STEAP2 Antibody shows potential for prostate cancer research.

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.