4RAK

Crystal structure of nuclear receptor subfamily 1, group h, member 2 (lxrb) complexed with partial agonist

Summary for 4RAK

• Entry DOI: 10.2210/pdb4rak/pdb
• Descriptor: Oxysterols receptor LXR-beta, 1,4-BUTANEDIOL, 2-{2-[2-(2-chlorophenyl)propan-2-yl]-1-[3'-(methylsulfonyl)biphenyl-4-yl]-1H-imidazol-4-yl}propan-2-ol, ... (4 entities in total)
• Functional Keywords: nhr, nr1h2, lxr-b, lxrb, unr, ner-i, rip15, ner, ligand binding domain, nuclear hormone receptor, rxr, transcription-agonist complex, transcription/agonist
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : P55055
• Total number of polymer chains: 2
• Total formula weight: 62374.19

Authors

Nanao, M. (deposition date: 2014-09-10, release date: 2014-12-31, Last modification date: 2024-02-28)

Primary citation

Kick, E.,Martin, R.,Xie, Y.,Flatt, B.,Schweiger, E.,Wang, T.L.,Busch, B.,Nyman, M.,Gu, X.H.,Yan, G.,Wagner, B.,Nanao, M.,Nguyen, L.,Stout, T.,Plonowski, A.,Schulman, I.,Ostrowski, J.,Kirchgessner, T.,Wexler, R.,Mohan, R.
Liver X Receptor (LXR) partial agonists: Biaryl pyrazoles and imidazoles displaying a preference for LXR beta.
Bioorg.Med.Chem.Lett., 25:372-377, 2015

PubMed Abstract: A series of biaryl pyrazole and imidazole Liver X Receptor (LXR) partial agonists has been synthesized displaying LXRβ selectivity. The LXRβ selective partial agonist 18 was identified with potent induction of ATP binding transporters ABCA1 and ABCG1 in human whole blood (EC50=1.2μM, 55% efficacy). In mice 18 displayed peripheral induction of ABCA1 at 3 and 10mpk doses with no significant elevation of plasma or hepatic triglycerides at these doses, showing an improved profile compared to a full pan-agonist.

PubMed: 25435151
DOI: 10.1016/j.bmcl.2014.11.029

Experimental method

X-RAY DIFFRACTION (2.04 Å)