5AYG

Crystal Structure of the Human ROR gamma Ligand Binding Domain With 3g

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.184 
  • R-Value Observed: 0.186 

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Ligand Structure Quality Assessment 


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


Literature

SAR Exploration Guided by LE and Fsp(3): Discovery of a Selective and Orally Efficacious ROR gamma Inhibitor

Hirata, K., Kotoku, M., Seki, N., Maeba, T., Maeda, K., Hirashima, S., Sakai, T., Obika, S., Hori, A., Hase, Y., Yamaguchi, T., Katsuda, Y., Hata, T., Miyagawa, N., Arita, K., Nomura, Y., Asahina, K., Aratsu, Y., Kamada, M., Adachi, T., Noguchi, M., Doi, S., Crowe, P., Bradley, E., Steensma, R., Tao, H., Fenn, M., Babine, R., Li, X., Thacher, S., Hashimoto, H., Shiozaki, M.

(2016) ACS Med Chem Lett 7: 23-27

  • DOI: https://doi.org/10.1021/acsmedchemlett.5b00253
  • Primary Citation of Related Structures:  
    5AYG

  • PubMed Abstract: 

    A novel series of RORγ inhibitors was identified starting with the HTS hit 1. After SAR investigation based on a prospective consideration of two drug-likeness metrics, ligand efficiency (LE) and fraction of sp(3) carbon atoms (Fsp(3)), significant improvement of metabolic stability as well as reduction of CYP inhibition was observed, which finally led to discovery of a selective and orally efficacious RORγ inhibitor 3z.

    • Organizational Affiliation: 

    Chemical Research Laboratories, Biological Pharmacological Research Laboratories, Drug Metabolism & Pharmacokinetics Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc. , 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Nuclear receptor ROR-gamma
A, B
258Homo sapiensMutation(s): 0 
Gene Names: RORC, NR1F3, RORG, RZRG
UniProt & NIH Common Fund Data Resources
Find proteins for P51449 (Homo sapiens)
Explore P51449 
Go to UniProtKB:  P51449
PHAROS:  P51449
GTEx:  ENSG00000143365 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP51449
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
4LQ
Query on 4LQ
Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]		3-[5-(2-cyclohexylethyl)-4-ethyl-1,2,4-triazol-3-yl]-N-naphthalen-1-yl-propanamide
C25 H32 N4 O
SZWIGRNIVUKPOZ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
4LQ BindingDB:  5AYG EC50: min: 300, max: 820 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.184 
  • R-Value Observed: 0.186 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 99.24α = 90
b = 99.24β = 90
c = 127.84γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-03-02
    Type: Initial release
  • Version 1.1: 2020-02-26
    Changes: Data collection, Derived calculations
  • Version 1.2: 2023-11-08
    Changes: Data collection, Database references, Refinement description