GI 254023X

GI 254023X is an inhibitor of the metalloproteinase-disintegrin ADAM10 (IC50 = 5.3 nM). 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, Cay-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-beta (1-42) (Abeta42, Cay-20574) in human brain microvessel endothelial cells (HBMECs) and increases Abeta42 transit across an in vitro blood brain barrier model in a concentration-dependent manner. In vivo, GI 254023X (200 mg/kg) reduces brain LRP1 shedding and increases plasma levels of Abeta40 in a mouse model of Alzheimer's disease.Formal Name: (alphaR)-N-[(1S)-2,2-dimethyl-1-[(methylamino)carbonyl]propyl]-alpha-[(1S)-1-(formylhydroxyamino)ethyl]-benzenepentanamide. CAS Number: 260264-93-5. Synonyms: GI 4023, SRI 028594. Molecular Formula: C21H33N3O4. Formula Weight: 391.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 1 mg/ml, Ethanol: 1 mg/ml, Ethanol:PBS (pH 7.2) (1:6): 0.14mg/ml. SMILES: C[C@H](N(C=O)O)[C@H](C(N[C@@H](C(C)(C)C)C(NC)=O)=O)CCCC1=CC=CC=C1. InChi Code: InChI=1S/C21H33N3O4/c1-15(24(28)14-25)17(13-9-12-16-10-7-6-8-11-16)19(26)23-18(20(27)22-5)21(2,3)4/h6-8,10-11,14-15,17-18,28H,9,12-13H2,1-5H3,(H,22,27)(H,23,26)/t15-,17+,18+/m0/s1. InChi Key: GHVMTHKJUAOZJP-CGTJXYLNSA-N.