GI 254023X is an inhibitor of the metalloproteinase-disintegrin ADAM10 (IC50 = 5.3 nM).1 It is selective for ADAM10 over ADAM17, matrix metalloproteinase-1 (MMP-1), and MMP-3 (IC50s = 541, 108, and 187 nM, respectively), but also inhibits MMP-9 and MMP-13 (IC50s = 2.5 and 1.1 nM, respectively). GI 254023X inhibits constitutive shedding of CX3CL1, but not shedding induced by phorbol 12-myristate 13-acetate (PMA; Item No. 10008014), in COS-7 cells transfected with human chemokines (IC50s = 0.4 and >10 μM, respectively). It also inhibits constitutive, but not PMA-induced, secretion of the IL-6 receptor (IL-6R) from THP-1 macrophages (IC50s = 1.8 and >10 μM, respectively). GX 254023X (1 μM) decreases shedding of low density lipoprotein receptor-related protein 1 (LRP1) induced by amyloid-β (1-42) (Aβ42; Item No. 20574) in human brain microvessel endothelial cells (HBMECs) and increases Aβ42 transit across an in vitro blood brain barrier model in a concentration-dependent manner.2 In vivo, GI 254023X (200 mg/kg) reduces brain LRP1 shedding and increases plasma levels of Aβ40 in a mouse model of Alzheimer’s disease.WARNING This product is not for human or veterinary use.