4L6S

PARP complexed with benzo[1,4]oxazin-3-one inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.167 

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Ligand Structure Quality Assessment 


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


Literature

Discovery of novel benzo[b][1,4]oxazin-3(4H)-ones as poly(ADP-ribose)polymerase inhibitors

Gangloff, A.R., Brown, J., de Jong, R., Dougan, D.R., Grimshaw, C.E., Hixon, M., Jennings, A., Kamran, R., Kiryanov, A., O'Connell, S., Taylor, E., Vu, P.

(2013) Bioorg Med Chem Lett 23: 4501-4505

  • DOI: https://doi.org/10.1016/j.bmcl.2013.06.055
  • Primary Citation of Related Structures:  
    4L6S

  • PubMed Abstract: 

    Structure based drug design of a series of novel 1,4-benzoxazin-3-one derived PARP-1 inhibitors are described. The synthesis, enzymatic & cellular activities and pharmacodynamic effects are described. Optimized analogs demonstrated inhibition of poly-ADP-ribosylation in SW620 tumor bearing nude mice through 24h following a single dose.

    • Organizational Affiliation: 

    Takeda California, 10410 Science Center Dr, San Diego, CA 92121, USA. [email protected]


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Poly [ADP-ribose] polymerase 1
A, B
353Homo sapiensMutation(s): 1 
Gene Names: ADPRT, PARP 1, PARP1, PPOL
EC: 2.4.2.30 (PDB Primary Data), 2.4.2 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for P09874 (Homo sapiens)
Explore P09874 
Go to UniProtKB:  P09874
PHAROS:  P09874
GTEx:  ENSG00000143799 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP09874
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
1WQ
Query on 1WQ
Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]		(2S)-6-{[4-(4-chlorophenyl)-3,6-dihydropyridin-1(2H)-yl]methyl}-2-methyl-2H-1,4-benzoxazin-3(4H)-one
C21 H21 Cl N2 O2
UXKGKMDPTXLNNA-AWEZNQCLSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
1WQ PDBBind:  4L6S IC50: 3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.167 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.525α = 90
b = 93.045β = 90
c = 165.193γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
AMoREphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

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: 2013-08-07
    Type: Initial release
  • Version 1.1: 2014-11-12
    Changes: Structure summary
  • Version 1.2: 2018-01-24
    Changes: Structure summary
  • Version 1.3: 2024-02-28
    Changes: Data collection, Database references, Derived calculations