Integrin Inhibitor

αvβ5 integrin-IN-1 (Compound 12) is a selective αvβ5 inhibitor (pIC₅₀ = 8.2). αvβ5 integrin-IN-1 exhibits 800-fold selectivity for αvβ5 versus αvβ3.

ICAM-1-IN-1 is a potent and selective inhibitor of E-selectin and ICAM-1 with IC₅₀ values of 7 and 5 nM, respectively.

Obtustatin is a non-RGD disintegrin consisting of 41 residues. Obtustatin inhibits the adhesion of α1β1 integrin to type IV Collagen (HY-NP003), blocks α1β1 integrin signaling in endothelial cells, and suppresses FGF2-induced angiogenesis. Obtustatin inhibits tumor progression in mouse models and upregulates VEGF expression in sarcoma-bearing mice. Obtustatin can be used in research related to Lewis lung carcinoma and S-180 sarcoma.

Isoxanthohumol is an orally active flavonoid compound. Isoxanthohumol has biological activities such as anti-tumor, anti-inflammatory, antioxidant, antiviral, antifungal, and inhibition of adipogenesis. Isoxanthohumol can induce apoptosis, autophagy, and migration of tumor cells. Isoxanthohumol is active against viruses such as HSV, BVDV, CMV, and Rhino. Isoxanthohumol can be used for the research of tumors, metabolic, and inflammatory diseases.

Irigenin is a is a lead compound, and mediates its anti-metastatic effect by specifically and selectively blocking α9β1 and α4β1 integrins binding sites on C-C loop of Extra Domain A (EDA). Irigenin shows anti-cancer properties. It sensitizes TRAIL-induced apoptosis via enhancing pro-apoptotic molecules in gastric cancer cells.

Synstatin (92-119) is an inhibitor of αvβ3/αvβ5 integrins and IGF1R with anti-angiogenic, anti-proliferative, antioxidant and anti-tumor activities. Synstatin (92-119) competitively blocks the capture of αvβ3/αvβ5 integrins and IGF1R by syndecan-1, disrupts the formation of the syndecan-1 : integrin : IGF1R ternary complex, inhibits integrin activation and talin-mediated signaling pathways, and blocks VEGF-induced angiogenesis. Synstatin (92-119) is applicable to research related to cancer and hepatocellular carcinoma.

Cenupatide (UPARANT) is a uPAR and FPR antagonist with anti-angiogenic, anti-inflammatory, and vascular barrier regulatory activities, as well as high stability and resistance to enzymatic degradation in blood/plasma. Cenupatide blocks the uPAR-FPR interaction, reduces VEGF-induced phosphorylation levels of AKT, VEGFR-2, STAT3, JNK, p38 MAPK, ERK1/2, and NF-κB p65, and inhibits αvβ3 integrin activation. Cenupatide suppresses endothelial cell migration, invasion, tube formation, and angiogenic signaling pathways, restores tight junctions and blood-retinal barrier integrity, reduces pro-inflammatory marker levels, and inhibits apoptosis. Cenupatide reduces retinal neovascularization, renal fibrosis, and vascular leakage, and restores visual function in preclinical models. Cenupatide is applicable to research related to retinopathy, diabetic complications, ocular diseases, cancer, and inflammatory diseases.

A20FMDV2 is a highly selective αvβ6 integrin inhibitor with human IC₅₀ values of 3 nM and binds with at least 1000-fold selectivity over other RGD-binding integrins. A20FMDV2 binds to the integrin’s RGD-binding site, induces rapid integrin internalization, and delays post-internalization integrin recycling to the cell surface. A20FMDV2 can be used for the research of pancreatic cancer, breast cancer, colorectal cancer, ovarian cancer, oral squamous cell carcinoma.

Phellopterin, an orally active furocoumarin with multiple biological activities. Phellopterin is a partial agonist of the central benzodiazepine receptors. Phellopterin exerts anti-inflammatory effects by upregulating SIRT1, downregulating ICAM-1 (reducing chronic inflammation, aiding diabetic ulcer healing), inhibiting STAT3 phosphorylation (easing atopic dermatitis inflammation), regulating Akt/PKC pathways (lowering TNF-α-induced VCAM-1 to block monocyte adhesion), and inhibiting TLR4/NF-κB pathway and macrophage M2 polarization (alleviating colitis-related cancers). Phellopterin suppresses ovarian cancer progression via inhibiting the PU.1/CLEC5A/PI3K-AKT loop (inducing cell cycle arrest, apoptosis, DNA damage). Phellopterin alleviates murine diabetes by promoting adipocyte differentiation and increasing PPARγ. Phellopterin also has anti-HSV-1 activity. Phellopterin can be used for studying anti-inflammation, anti-cancer (e.g., ovarian cancer, colitis cancer), blood glucose lowering, anti-diabetes, and anti-virus.

A-286982 is a potent and allosteric LFA-1/ICAM-1 interaction inhibitor with IC₅₀s of 44 nM and 35 nM in an LFA-1/ICAM-1 binding and LFA-1-mediated cellular adhesion assay, respectively.

Obtustatin triacetate is a 41-residue non-RGD disintegrin. Obtustatin triacetate can be isolated from the venom of Vipera lebetina obtusa. Obtustatin triacetate is a potent and selective inhibitor of integrin α1β1 adhesion to type IV collagen. Obtustatin triacetate inhibits angiogenesis and may be used in cancer research.

BIO-1211 is a highly selective and orally active α4β1 (VLA-4) inhibitor, with IC₅₀ values of 4 nM and 2 μM for α4β1 and α4β7, respectively.

Cyclo(RGDyK) trifluoroacetate is a potent and selective α_Vβ₃ integrin inhibitor with an IC₅₀ of 20 nM.

ST6GAL1-IN-1 is an orally active selective ST6GAL1 inhibitor (IC₅₀ = 20 μM). ST6GAL1-IN-1 exhibits high antimetastatic potential, effectively inhibiting the migration of MDA-MB-231 cells at noncytotoxic concentrations. ST6GAL1-IN-1 can disrupt integrin sialylation in MDA-MB-231 cells. ST6GAL1-IN-1 inhibits tumor angiogenesis and cancer metastasis via the Integrin/VEGFR2-mediated signaling pathway. ST6GAL1-IN-1 effectively suppresses both tumor growth and cancer metastasis on the MDA-MB-231 xenograft model. ST6GAL1-IN-1 can be used for the study of Triple-negative breast cancer (TNBC).

MNS (NSC 170724), the beta-nitrostyrene derivative, is an orally active tyrosine kinase inhibitor, a broad-spectrum antiplatelet agent, and a PANoptosis inhibitor. MNS inhibits Src, Syk, and FAK with IC₅₀ of 27.3, 2.8, and 97.6 μM, respectively. MNS inhibits NLRP3 inflammasome and β1 integrin. MNS completely inhibits U46619, ADP-, arachidonic acid-, collagen-, and thrombin-induced platelet aggregation with IC₅₀ values of 2.1, 4.1, 5.8, 7.0, and 12.7 μM, respectively. MNS is cytotoxic to a variety of cells.

BIO5192 hydrate is a selective and potent integrin α4β1 (VLA-4) inhibitor (K_d<10 pM). BIO5192 hydrate selectively binds to α4β1 (IC₅₀=1.8 nM) over a range of other integrins. BIO5192 hydrate results in a 30-fold increase in mobilization of murine hematopoietic stem and progenitors (HSPCs) over basal levels.

STX-100 (BG00011) is a humanized monoclonal antibody targeting αVβ6 integrin. STX-100 specifically binds αVβ6 integrin, blocks latent TGF-β activation via latency-associated peptide (LAP) interaction prevention, and reduces profibrotic responses. STX-100 can be used for the research of idiopathic pulmonary fibrosis, and cancer.

PLN-1474 (compound 1) is an orally active and selective ανβ1 integrin inhibitor with an IC50 value of <50 nM. PLN-1474 reduces levels of pSMAD3/SMAD3 in liver, hepatic collagen gene expression and hepatic OHP concentration in liver fibrosis mouse model. PLN-1474 can be used for the research of preventing, delaying or researching a fibrotic or cirrhotic disease or disorder.

EMD527040 is a potent and highly selective αvβ6 antagonist with antifibrotic activities. EMD527040 can be used for carcinoma and liver fibrosis research.

Intetumumab (CNTO 95) is a human monoclonal antibody targeting αv integrin, with a K_d value of 1-24 nM. Through high-affinity binding to αv integrin, Intetumumab inhibits its interaction with extracellular matrix proteins (such as vitronectin and fibronectin), thereby blocking the downstream focal adhesion kinase signaling pathway. This further inhibits the adhesion, migration and invasion of tumor cells as well as the proliferation of vascular endothelial cells, promotes cell apoptosis, and exerts anti-tumor and anti-angiogenic effects. Intetumumab can be used in research related to head and neck cancer, non-small cell lung cancer and uterine serous papillary carcinoma.