3l0e
X-ray crystal structure of a Potent Liver X Receptor ModulatorX-ray crystal structure of a Potent Liver X Receptor Modulator
Structural highlights
FunctionNR1H2_HUMAN Orphan receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedTertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor. Discovery of Tertiary Sulfonamides as Potent Liver X Receptor Antagonists.,Zuercher WJ, Buckholz RG, Campobasso N, Collins JL, Galardi CM, Gampe RT, Hyatt SM, Merrihew SL, Moore JT, Oplinger JA, Reid PR, Spearing PK, Stanley TB, Stewart EL, Willson TM J Med Chem. 2010 Mar 26. PMID:20345102[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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