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TP508 is a 23 amino acid synthetic peptide representing residues 508-530 of human prothrombin which is identified as a potential receptor-binding domain based on competition for high-affinity thrombin binding to fibroblasts.

TP508 treatment reverses radiation effects on NO signaling, restores tube formation and accelerates the repair of radiation-induced DSB in irradiated human endothelial cells[1]. TP508 injection increases responsiveness of endothelial cells from aortic explants to VEGF-stimulated angiogenesis in vitro. TP508 stimulation does not significantly affect the VEGF mRNA levels in normoxic or hypoxic cells[2]. TP508 acts as an antagonist for the effects of thrombin. TP508 peptide inhibits these thrombin-induced effects through a RGD and αvβ3-related mechanism[4].

TP508 (500 μg) in sham-irradiated animals significantly increases the amount of endothelial cell sprouting from aortic explants. TP508 significantly increases the sprouting in sham-irradiated and irradiated animals, more than doubling the amount of sprouting in explants from animals at all exposure doses. TP508 (10 mg/kg) given 24 h after 8.5 Gy gamma irradiation significantly increases 30-day survival in mice, from 26.7 to 73.3%[1]. TP508 injection increases endothelial sprouting and potentiates VEGF-stimulated angiogenesis[2]. In type I diabetic swine, TP508 (1 mg/kg, infusion) reduces infarct size after IR[3].

[1]. Olszewska-Pazdrak B, et al. Nuclear Countermeasure Activity of TP508 Linked to Restoration of Endothelial Function and Acceleration of DNA Repair. Radiat Res. 2016 Aug;186(2):162-74. [2]. Olszewska-Pazdrak B, et al. Systemic administration of thrombin peptide TP508 enhances VEGF-stimulated angiogenesis and attenuates effects of chronic hypoxia. J Vasc Res. 2013;50(3):186-9 [3]. Chu LM, et al. Effect of thrombin fragment (TP508) on myocardial ischemia reperfusion injury in a model of type 1 diabetes mellitus. Circulation. 2010 Sep 14;122(11 Suppl):S162-9. [4]. Tsopanoglou NE, et al. On the mode of action of thrombin-induced angiogenesis: thrombin peptide, TP508, mediates effects in endothelial cells via alphavbeta3 integrin. Thromb Haemost. 2004 Oct;92(4):846-57.

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