4RAK

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

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.04 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.232 

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This is version 1.2 of the entry. See complete history. 


Literature

Liver X Receptor (LXR) partial agonists: Biaryl pyrazoles and imidazoles displaying a preference for LXR beta.

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.

(2015) Bioorg Med Chem Lett 25: 372-377

  • DOI: https://doi.org/10.1016/j.bmcl.2014.11.029
  • Primary Citation of Related Structures:  
    4RAK

  • 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.

    • Organizational Affiliation: 

    Discovery Chemistry, Research & Development, Bristol-Myers Squibb, PO Box 5400, Princeton, NJ 08543-5400, United States. Electronic address: ellen.kick@bms.com.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Oxysterols receptor LXR-beta
A, B
264Homo sapiensMutation(s): 0 
Gene Names: NR1H2, LXRB, NER, UNR
UniProt & NIH Common Fund Data Resources
Find proteins for P55055 (Homo sapiens)
Explore P55055 
Go to UniProtKB:  P55055
PHAROS:  P55055
GTEx:  ENSG00000131408 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP55055
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
652 Binding MOAD:  4RAK Ki: 14 (nM) from 1 assay(s)
BindingDB:  4RAK EC50: min: 33, max: 1200 (nM) from 5 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.04 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.232 
  • Space Group: I 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.82α = 90
b = 120.63β = 90
c = 176.25γ = 90
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

  • Released Date: 2014-12-31 
    • Deposition Author(s): Nanao, M.

Revision History  (Full details and data files)

  • Version 1.0: 2014-12-31
    Type: Initial release
  • Version 1.1: 2015-01-14
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations