Echistatin

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^[1][2][3][4]. In Vitro:Echistatin (100 μg/mL; 15 min-3 h) reduces the phosphorylation level of pp125^FAK Tyr³⁹⁷ in fibronectin-adherent B16-BL6 mouse melanoma cells; decreases the binding level of pp125^FAK to paxillin in a time-dependent manner; and inhibits the autophosphorylation of pp125^FAK, the phosphorylation of paxillin, and the binding level of pp125^FAK to pp60^src[1].
Echistatin (100 μg/mL; 30 min) induces detachment of fibronectin-adherent B16-BL6 mouse melanoma cells and causes loss of pp125^FAK and paxillin from focal adhesions^[1].
Echistatin (10 nCi/tube; 1 h) binds specifically to α_vβ₃ integrin in membrane fractions enriched from mouse osteoclast-like cells, with an IC₅₀ of 0.6 nM, and this binding is selectively blocked by anti-α_vβ₃ integrin antibody^[2].
Echistatin (100 nM; 7 days, days 0-4, days 4-7) potently inhibits the formation of TRAP-positive multinucleated osteoclast-like cells in a mouse MB1.8 cell-bone marrow co-culture system, with an IC₅₀ of 0.7 nM^[2].
Echistatin (10^-11 to 10^-8 M; 15 h) inhibits M-CSF-induced fusion of mouse mononuclear pre-fusion osteoclasts with an IC₅₀ of 0.6 nM, and inhibits M-CSF-induced migration of mouse mononuclear pre-fusion osteoclasts with an IC₅₀ of 1.0 nM^[2].
Echistatin enables the quantitative detection of Echistatin levels in biological samples via competitive receptor binding assays, in which Echistatin extracts from HEK 293 cells overexpressing αvβ3 integrin displace radiolabeled Echistatin^[3].
Echistatin (0.1-20 μg/mL; 10 min-6 days) is a reversible, non-cytotoxic inhibitor that suppresses the adhesion of Lewis lung carcinoma (3LL) cells to immobilized fibronectin and laminin in vitro^[4]. In Vivo:Echistatin (30 µg/kg/min; subcutaneous; continuous infusion; 3 days) inhibits bone resorption in mice with secondary hyperparathyroidism, preserves trabecular bone volume and structure, blocks the progression of enhanced bone turnover, and increases the number of osteoclasts without detectable changes in osteoclast morphology^[3].
Echistatin (6-30 µg/kg/min; subcutaneous injection; continuous infusion; 6 h) inhibits the acute calcemic response to exogenous PTH in parathyroidectomized mice^[3].
Echistatin (20 μg；intramuscular injection; co-injected once together with tumor cells) co-administrated with 2.5 × 10⁵ 3LL cells via intramuscular injection suppresses tumor growth and metastasis of Lewis lung carcinoma in male C57BL/6NCrlBR mice^[4].
Echistatin (1 μg/g; intraperitoneal injection; once every 72 hours; 4 doses total) inhibits Lewis lung cancer tumor growth and metastasis formation in male C57BL/6NCrlBR mice^[4].