3L0E

X-ray crystal structure of a Potent Liver X Receptor Modulator

Summary for 3L0E

• Entry DOI: 10.2210/pdb3l0e/pdb
• Related: 1P8D 1PQ6 1PQ9 1UPV
• Descriptor: Oxysterols receptor LXR-beta, Nuclear receptor coactivator 2, N-(2-chloro-6-fluorobenzyl)-1-methyl-N-{[3'-(methylsulfonyl)biphenyl-4-yl]methyl}-1H-imidazole-4-sulfonamide, ... (4 entities in total)
• Functional Keywords: hlxr-beta, human liver x receptor-beta, sulfonamide modulator, dna-binding, metal-binding, nucleus, receptor, transcription, transcription regulation, zinc-finger, activator, phosphoprotein
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : P55055 Q15596
• Total number of polymer chains: 2
• Total formula weight: 30738.47

Authors

Gampe Jr., R.T. (deposition date: 2009-12-09, release date: 2010-04-07, Last modification date: 2023-09-06)

Primary citation

Zuercher, W.J.,Buckholz, R.G.,Campobasso, N.,Collins, J.L.,Galardi, C.M.,Gampe, R.T.,Hyatt, S.M.,Merrihew, S.L.,Moore, J.T.,Oplinger, J.A.,Reid, P.R.,Spearing, P.K.,Stanley, T.B.,Stewart, E.L.,Willson, T.M.
Discovery of tertiary sulfonamides as potent liver X receptor antagonists.
J.Med.Chem., 53:3412-3416, 2010

PubMed Abstract: Tertiary 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.

PubMed: 20345102
DOI: 10.1021/jm901797p

Experimental method

X-RAY DIFFRACTION (2.3 Å)