5EM5

EGFR kinase domain mutant "TMLR" with pyridone compound 2: 4-[2-(4-chlorophenyl)ethylamino]-~{N}-[4-(4-methylpiperazin-1-yl)phenyl]-2-oxidanylidene-1~{H}-pyridine-3-carboxamide

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.213 

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This is version 1.3 of the entry. See complete history. 


Literature

Pyridones as Highly Selective, Noncovalent Inhibitors of T790M Double Mutants of EGFR.

Bryan, M.C., Burdick, D.J., Chan, B.K., Chen, Y., Clausen, S., Dotson, J., Eigenbrot, C., Elliott, R., Hanan, E.J., Heald, R., Jackson, P., La, H., Lainchbury, M., Malek, S., Mann, S.E., Purkey, H.E., Schaefer, G., Schmidt, S., Seward, E., Sideris, S., Wang, S., Yen, I., Yu, C., Heffron, T.P.

(2016) ACS Med Chem Lett 7: 100-104

  • DOI: https://doi.org/10.1021/acsmedchemlett.5b00428
  • Primary Citation of Related Structures:  
    5EM5, 5EM6, 5EM7, 5EM8

  • PubMed Abstract: 

    The rapid advancement of a series of noncovalent inhibitors of T790M mutants of EGFR is discussed. The optimization of pyridone 1, a nonselective high-throughput screening hit, to potent molecules with high levels of selectivity over wtEGFR and the broader kinome is described herein.

    • Organizational Affiliation: 

    Genentech , South San Francisco, California 94080, United States.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Epidermal growth factor receptor331Homo sapiensMutation(s): 5 
Gene Names: EGFR, ERBB, ERBB1, HER1
EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for P00533 (Homo sapiens)
Explore P00533 
Go to UniProtKB:  P00533
PHAROS:  P00533
GTEx:  ENSG00000146648 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00533
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
5Q2
Query on 5Q2
Download Ideal Coordinates CCD File 
B [auth A]4-[2-(4-chlorophenyl)ethylamino]-~{N}-[4-(4-methylpiperazin-1-yl)phenyl]-2-oxidanylidene-1~{H}-pyridine-3-carboxamide
C25 H28 Cl N5 O2
MOSAREMUBHMKIV-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.213 
  • Space Group: I 2 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 148.968α = 90
b = 148.968β = 90
c = 148.968γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
HKL-2000data reduction
SCALEPACKdata 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: 2015-12-30
    Type: Initial release
  • Version 1.1: 2016-02-10
    Changes: Database references
  • Version 1.2: 2017-09-06
    Changes: Data collection, Derived calculations
  • Version 1.3: 2024-03-06
    Changes: Data collection, Database references