αvβ3 Antagonist

Cilengitide (EMD 121974) is a BBB-permeable integrins antagonist with IC₅₀s of 0.61 nM (α_νβ₃), 8.4 nM (α_νβ₅) and 14.9 nM (α₅β₁), respectively. Cilengitide inhibits the binding of α_νβ₃ and α_νβ₅ to Vitronectin with IC₅₀s of 4 nM and 79 nM, respectively. Cilengitide inhibits TGF-β/Smad signaling, mediates PD-L1 expression. Cilengitide also induces apoptosis, shows antiangiogenic effect in the research against glioblastoma and other cancers.

ATN-161 is an antagonist of α5β1 integrin and αvβ3 integrin, as well as an inhibitor of fibrosis, an inhibitor of oxidative stress, a tight junction stabilizer, a mitochondrial integrity protector, an angiogenesis inhibitor and an antiviral agent. ATN-161 inhibits NLRP3, MAPK, and ROS. ATN-161 protects mice from SARS-CoV-2 infection. ATN-161 reduces infarct volume, alleviates edema, decreases immune cell infiltration, reduces the area of choroidal neovascularization lesions, lowers tumor microvessel density and viral load. ATN-161 can be used in research related to ischemic stroke, choroidal neovascularization, breast cancer, coronavirus disease 2019 (COVID-19), and liver metastasis of colorectal cancer.

MK-0429 (L-000845704) is an orally active, potent, selective and nonpeptide pan-integrin antagonist with IC₅₀ values of 1.6 nM, 2.8 nM, 0.1 nM, 0.7 nM, 0.5 nM and 12.2 nM for αvβ1, αvβ3, αvβ5, αvβ6, αvβ8 and α5β1, respectively.

SU015 (DOTA-RGDfK dimer) is a Integrin α_vβ₅ and α_vβ₃ antagonist. SU015 exhibits comparable affinity for α_vβ₅ and α_vβ₃, with relatively higher potency and specificity compared to other integrins. SU015 inhibits α_vβ₃-mediated cell adhesion to fibrinogen, α_vβ₃-mediated adhesion of activated platelets to osteopontin, and α_vβ₅-mediated cell adhesion to vitronectin. SU015 shows potent inhibitory effects on FGF2-induced angiogenesis in the CAM model. SU015 carries a linker arm available for radioisotope conjugation, and acts as a target-specific radioreagent when labeled with ⁹⁰Y (i.e., RP697) or ¹⁷⁷Lu (i.e., RP688). SU015 can be used in studies related to tumor metastasis and tumors.

SB-273005 is an orally active non-peptide αvβ3 integrin antagonist with K_i values of 1.2 nM and 0.3 nM for αvβ3 and αvβ5, respectively. SB-273005 blocks the binding of integrins to the RGD sequence in the extracellular matrix. SB-273005 inhibits Rictor phosphorylation and reduces IL-10 secretion. SB-273005 inhibits inflammation, prevents bone loss, regulates vascular smooth muscle function, and reverses pregnancy-induced immune deviation. SB-273005 can be used in the study of rheumatoid arthritis, osteoporosis, and aneurysms. .

GSK 3008348 is a small molecule antagonist of integrin αvβ6 with IC₅₀ values for αvβ6, αvβ1, αvβ3, αvβ5, and αvβ8 are 1.50, 2.83, 12.53, 4.00, and 2.26 nM, respectively. GSK 3008348 can target the αvβ6 integrin, inhibit TGF-β activation, and thereby alleviate the fibrotic process. GSK 3008348 prevents the binding of the foot-and-mouth disease virus (FMDV) to the αvβ6 integrin receptor on the surface of host cells, thereby inhibiting the entry of the virus. GSK 3008348 can be used for research on pulmonary fibrosis and various types of cancer.

GSK 3008348 hydrochloride is a small molecule antagonist of integrin αvβ6 with IC₅₀ values for αvβ6, αvβ1, αvβ3, αvβ5, and αvβ8 are 1.50, 2.83, 12.53, 4.00, and 2.26 nM, respectively. GSK 3008348 hydrochloride can target the αvβ6 integrin, inhibit TGF-β activation, and thereby alleviate the fibrotic process. GSK 3008348 hydrochloride prevents the binding of the foot-and-mouth disease virus (FMDV) to the αvβ6 integrin receptor on the surface of host cells, thereby inhibiting the entry of the virus. GSK 3008348 hydrochloride can be used for research on pulmonary fibrosis and various types of cancer.

HSDVHK-NH2 is an antagonist of the integrin αvβ3-vitronectin interaction, with an IC₅₀ of 1.74 pg/mL (2.414 pM).

Echistatin is a naturally derived RGD-containing snake venom peptide. Echistatin exhibits an IC₅₀ of 0.6 nM against mouse α_vβ₃ integrin, and acts as an antagonist against α_vβ₃, α_IIbβ₃, α₅β₁ integrins, pp125^FAK and paxillin. Echistatin reduces the phosphorylation of pp125^FAK and paxillin, inhibits the autophosphorylation and kinase activity of pp125^FAK, and weakens its binding to pp60^src and paxillin. Echistatin disrupts the actin cytoskeleton and focal adhesions, induces melanoma cell detachment from fibronectin, and regulates cell adhesion and motility. Echistatin inhibits osteoclast maturation and migration, bone resorption, platelet aggregation, bone loss, as well as adhesion and metastasis of Lewis lung cancer cells; it also increases the number of osteoclasts and bone coverage area in mice with secondary hyperparathyroidism. Echistatin can be used in research related to melanoma, lung cancer and secondary hyperparathyroidism.

Echistatin TFA is a naturally derived RGD-containing snake venom peptide. Echistatin TFA exhibits an IC₅₀ of 0.6 nM against mouse α_vβ₃ integrin, and acts as an antagonist against α_vβ₃, α_IIbβ₃, α₅β₁ integrins, pp125^FAK and paxillin. Echistatin TFA reduces the phosphorylation of pp125^FAK and paxillin, inhibits the autophosphorylation and kinase activity of pp125^FAK, and weakens its binding to pp60^src and paxillin. Echistatin TFA disrupts the actin cytoskeleton and focal adhesions, induces melanoma cell detachment from fibronectin, and regulates cell adhesion and motility. Echistatin TFA inhibits osteoclast maturation and migration, bone resorption, platelet aggregation, bone loss, as well as adhesion and metastasis of Lewis lung cancer cells; it also increases the number of osteoclasts and bone coverage area in mice with secondary hyperparathyroidism. Echistatin TFA can be used in research related to melanoma, lung cancer and secondary hyperparathyroidism.

Nesvategrast (SF0166) is a potent and selective α_vβ₃ antagonist with IC₅₀ values of 0.6 nM, 8 nM, and 13 nM for α_vβ₃, α_vβ₆, and α_vβ₈, respectively. Nesvategrast inhibits cellular adhesion to vitronectin across human, rat, rabbit, and dog cell lines with IC₅₀ values of 7.6 pM to 76 nM. Nesvategrast decreases neovascularization in the oxygen-induced retinopathy mouse model.

JNJ-26076713 is a potent and orally active alpha V integrin antagonist with IC₅₀ values of 2.3 nM and 6.3 nM for alpha(V)beta(3) and alpha(V)beta(5), respectively. JNJ-26076713 inhibits retinal neovascularization.