5T2L

mPI3Kd IN COMPLEX WITH 7l


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.55 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.228 
  • R-Value Observed: 0.230 

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Ligand Structure Quality Assessment 


This is version 1.0 of the entry. See complete history


Literature

Discovery of triazole aminopyrazines as a highly potent and selective series of PI3K delta inhibitors.

Terstiege, I.Perry, M.Petersen, J.Tyrchan, C.Svensson, T.Lindmark, H.Oster, L.

(2017) Bioorg Med Chem Lett 27: 679-687

  • DOI: https://doi.org/10.1016/j.bmcl.2016.11.004
  • Primary Citation of Related Structures:  
    5T23, 5T27, 5T28, 5T2B, 5T2D, 5T2G, 5T2I, 5T2L, 5T2M

  • PubMed Abstract: 

    A novel class of potent PI3Kδ inhibitors with >1000-fold selectivity against other class I PI3K isoforms is described. Optimization of the substituents on a triazole aminopyrazine scaffold, emerging from an in-house PI3Kα program, turned moderately selective PI3Kδ compounds into highly potent and selective PI3Kδ inhibitors. These efforts resulted in a series of aminopyrazines with PI3Kδ IC 50 ⩽1nM in the enzyme assay, some of the most selective PI3Kδ inhibitors published to date, with a cell potency in a JeKo-cell assay of 20-120nM.


  • Organizational Affiliation

    Respiratory, Inflammation & Autoimmunity, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal, 43183, Sweden. Electronic address: Ina.Terstiege@astrazeneca.com.


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 isoform939Mus 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
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
74H
Query on 74H

Download Ideal Coordinates CCD File 
B [auth A]1-[3-azanyl-6-[1-methyl-5-(1-phenylcyclopropyl)-1,2,4-triazol-3-yl]pyrazin-2-yl]pyrazole-3-carboxamide
C20 H19 N9 O
PPNTYGOEVAXAOA-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
74H BindingDB:  5T2L IC50: 63 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.55 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.228 
  • R-Value Observed: 0.230 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.554α = 90
b = 142.189β = 90
c = 218.768γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
MOSFLMdata reduction
SCALAdata scaling
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-04-19
    Type: Initial release