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Overview
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Background
EG00229 is a small molecule inhibitor of neuropilin-1(Nrp1) with an IC50 of 3μM [1].EG00229 has been reported to inhibit VEGF-A binding to PAE/NRP1 in the Nrp1and bt-VEGF-A binding to purified Nrp1 b1 domain in a cell-free assay with an IC50 value of 8μM and 3μM, respectively. In addition, EG00229 has also shown the inhibition of VEGF-A binding to VEGFR2, VEGFR1 and Nrp1 in human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner with an IC50 value of 23μM [1]. Besides, EG00229 has been revealed to prevent tuftsin binding to the Nrp1 which is at the cell surface. Moreover, EG00229 has been noted to suppress the anti-inflammatory M2 shift in microglia induced by tuftsin and thus potently prevent tuftsin’s action [2].
[1] Jarvis A1, Allerston CK, Jia H, Herzog B, Garza-Garcia A, Winfield N, Ellard K, Aqil R, Lynch R, Chapman C, Hartzoulakis B, Nally J, Stewart M, Cheng L, Menon M, Tickner M, Djordjevic S, Driscoll PC, Zachary I, Selwood DL.Small molecule inhibitors of the neuropilin-1 vascular endothelial growth factor A (VEGF-A) interaction. J Med Chem. 2010 Mar 11;53(5):2215-26.
[2] Nissen JC1, Selwood DL, Tsirka SE. Tuftsin signals through its receptor neuropilin-1 via the transforming growth factor beta pathway. J Neurochem. 2013 Nov;127(3):394-402.
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