An ADAM17/TACE and ADAM10 inhibitor
GW 280264X is an inhibitor of disintegrin and metalloproteinase domain-containing protein 17/TNF-α converting enzyme (ADAM17/TACE) and ADAM10 (IC50s = 8 and 11.5 nM, respectively).1 It inhibits TNF-α-induced cleavage of endomucin in human umbilical vein endothelial cells (HUVECs) when used at a concentration of 10 µM.2 GW 280264X (1 and 10 µM) inhibits angiotensin-converting enzyme 2 (ACE2) ectodomain shedding induced by phorbol 12-myristate 13-acetate in HEK-ACE2 cells.3 It reduces ACE2 shedding and prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in HK-2 cells.4
1.Hundhausen, C., Misztela, D., Berkout, T.A., et al.The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesionBlood102(4)1186-1195(2003) 2.Yang, J., LeBlanc, M.E., Cano, I., et al.ADAM10 and ADAM17 proteases mediate proinflammatory cytokine-induced and constitutive cleavage of endomucin from the endothelial surfaceJ. Biol. Chem.295(19)6641-6651(2020) 3.Lambert, D.W., Yarski, M., Warner, F.J., et al.Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2)J. Biol. Chem.280(34)30113-30119(2005) 4.Yeung, M.L., Teng, J.L.L., Jia, L., et al.Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin systemCell1841-17(2021)
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