6Q73

PI3K delta in complex with N[2chloro5(3,6dihydro2Hpyran4yl)pyridin3yl]methanesulfonamide

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.21 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.176 

wwPDB Validation   3D Report Full Report


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


Literature

Discovery of Potent, Efficient, and Selective Inhibitors of Phosphoinositide 3-Kinase delta through a Deconstruction and Regrowth Approach.

Barton, N., Convery, M., Cooper, A.W.J., Down, K., Hamblin, J.N., Inglis, G., Peace, S., Rowedder, J., Rowland, P., Taylor, J.A., Wellaway, N.

(2018) J Med Chem 61: 11061-11073

  • DOI: https://doi.org/10.1021/acs.jmedchem.8b01556

  • PubMed Abstract: 

    A deconstruction of previously reported phosphoinositide 3-kinase δ (PI3Kδ) inhibitors and subsequent regrowth led to the identification of a privileged fragment for PI3Kδ, which was exploited to deliver a potent, efficient, and selective lead series with a novel binding mode observed in the PI3Kδ crystal structure.

    • Organizational Affiliation: 

    GlaxoSmithKline R&D, Medicines Research Centre , Gunnels Wood Road , SG1 2NY Stevenage , U.K.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform940Mus musculusMutation(s): 0 
Gene Names: Pik3cd
EC: 2.7.1.153
UniProt
Find proteins for O35904 (Mus musculus)
Explore O35904 
Go to UniProtKB:  O35904
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO35904
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
HKK (Subject of Investigation/LOI)
Query on HKK
Download Ideal Coordinates CCD File 
B [auth A]~{N}-[2-chloranyl-5-(3,6-dihydro-2~{H}-pyran-4-yl)pyridin-3-yl]methanesulfonamide
C11 H13 Cl N2 O3 S
PGVPPOVJVOILFT-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.21 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.176 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 141.77α = 90
b = 64.25β = 102.58
c = 116.32γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
autoPROCdata scaling
BUSTERphasing

Structure Validation

View Full Validation Report



View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-12-26
    Type: Initial release
  • Version 1.1: 2019-04-24
    Changes: Data collection, Database references
  • Version 1.2: 2021-09-29
    Changes: Data collection, Database references, Refinement description