3FC6

hRXRalpha & mLXRalpha with an indole Pharmacophore, SB786875

PDB DOI: https://doi.org/10.2210/pdb3FC6/pdb

Classification: TRANSCRIPTION
Organism(s): Homo sapiens, Mus musculus
Mutation(s): No

Deposited: 2008-11-21 Released: 2009-02-10
Deposition Author(s): Washburn, D.G., Hoang, T.H., Campobasso, N., Smallwood, A., Parks, D.J., Webb, C.L., Frank, K., Nord, M., Duraiswami, C., Evans, C., Jaye, M., Thompson, S.K.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.06 Å
R-Value Free: 0.250
R-Value Work: 0.199
R-Value Observed: 0.201

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Synthesis and SAR of potent LXR agonists containing an indole pharmacophore.

Washburn, D.G., Hoang, T.H., Campobasso, N., Smallwood, A., Parks, D.J., Webb, C.L., Frank, K.A., Nord, M., Duraiswami, C., Evans, C., Jaye, M., Thompson, S.K.

(2009) Bioorg Med Chem Lett 19: 1097-1100

PubMed: 19167885 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2009.01.004
Primary Citation of Related Structures:
3FC6

PubMed Abstract:
A novel series of 1H-indol-1-yl tertiary amine LXR agonists has been designed. Compounds from this series were potent agonists with good rat pharmacokinetic parameters. In addition, the crystal structure of an LXR agonist bound to LXRalpha will be disclosed.

Organizational Affiliation

Department of Chemistry, Molecular Discovery Research, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA. [email protected]

Macromolecule Content

Total Structure Weight: 117.31 kDa
Atom Count: 7,497
Modelled Residue Count: 891
Deposited Residue Count: 1,016
Unique protein chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Retinoic acid receptor RXR-alpha	A, C	242	Homo sapiens	Mutation(s): 0
UniProt & NIH Common Fund Data Resources
Find proteins for P19793 (Homo sapiens) Explore P19793 Go to UniProtKB: P19793
PHAROS: P19793 GTEx: ENSG00000186350
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P19793
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Nr1h3 protein	B, D	266	Mus musculus	Mutation(s): 0
UniProt & NIH Common Fund Data Resources
Find proteins for Q9Z0Y9 (Mus musculus) Explore Q9Z0Y9 Go to UniProtKB: Q9Z0Y9
IMPC: MGI:1352462
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q9Z0Y9
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
LX2 Query on LX2 Download Ideal Coordinates CCD File SDF format, chain F [auth B] SDF format, chain H [auth D] MOL2 format, chain F [auth B] MOL2 format, chain H [auth D] mmCIF format, chain F [auth B] mmCIF format, chain H [auth D]	F [auth B], H [auth D]	[4-(3-{[2-chloro-3-(trifluoromethyl)benzyl](2,2-diphenylethyl)amino}propoxy)-1H-indol-1-yl]acetic acid C₃₅ H₃₂ Cl F₃ N₂ O₃ RHWNXOWPCIQOAH-UHFFFAOYSA-N		Interactions Focus chain F [auth B] Focus chain H [auth D] Interactions & Density Focus chain F [auth B] Focus chain H [auth D]
REA Query on REA Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain G [auth C] MOL2 format, chain E [auth A] MOL2 format, chain G [auth C] mmCIF format, chain E [auth A] mmCIF format, chain G [auth C]	E [auth A], G [auth C]	RETINOIC ACID C₂₀ H₂₈ O₂ SHGAZHPCJJPHSC-YCNIQYBTSA-N		Interactions Focus chain E [auth A] Focus chain G [auth C] Interactions & Density Focus chain E [auth A] Focus chain G [auth C]

Binding Affinity Annotations
ID	Source	Binding Affinity
REA	BindingDB: 3FC6	IC50: min: 5.00e+4, max: 5.00e+4 (nM) from 3 assay(s)
LX2	BindingDB: 3FC6	EC50: 14 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.06 Å
R-Value Free: 0.250
R-Value Work: 0.199
R-Value Observed: 0.201
Space Group: C 1 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 122.162	α = 90
b = 90.029	β = 111.92
c = 101.642	γ = 90

Software Package:

Software Name	Purpose
HKL-2000	data collection
MLPHARE	phasing
PHENIX	refinement
HKL-2000	data reduction
SCALEPACK	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2009-02-10

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2009-02-10
Type: Initial release
Version 1.1: 2011-07-13
Changes: Version format compliance
Version 1.2: 2023-12-27
Changes: Data collection, Database references, Derived calculations