6uf0 | pdb_00006uf0

Crystal structure of N-(4-((4-methoxy-N-(2,2,2-trifluoroethyl)phenyl)sulfonamido)isoquinolin-1-yl)-N-((4-methoxyphenyl)sulfonyl)glycine bound to human Keap1 Kelch domain

spinqualitylabelsall models 6uf0, resolution 1.96Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6uf0 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: DMS, FMT, NA, Q5V, Q5Y Gene: KEAP1, INRF2, KIAA0132, KLHL19 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Pharmacological activation of NRF2 (nuclear factor erythroid 2-related factor 2) arises from blocking the interaction of NRF2 with its negative regulator, KEAP1 (Kelch-like ECH-associated protein 1). We previously reported an isoquinoline-based NRF2 activator, but this compound showed negative logD7.4 and a -2 charge at physiological pH, which may have limited its membrane permeability. In this work, we report potent, metabolically stable analogs that result from replacing a carboxymethyl group at the 4-position with a fluoroalkyl group. Isoquinoline Kelch-like ECH-Associated Protein 1-Nuclear Factor (Erythroid-Derived 2)-like 2 (KEAP1-NRF2) Inhibitors with High Metabolic Stability.,Lazzara PR, David BP, Ankireddy A, Richardson BG, Dye K, Ratia KM, Reddy SP, Moore TW J Med Chem. 2019 Nov 14. doi: 10.1021/acs.jmedchem.9b01074. PMID:31682434 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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