4FF8

Inhibitor bound structure of the kinase domain of the murine receptor tyrosine kinase TYRO3 (Sky)

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.324 
  • R-Value Work: 0.277 
  • R-Value Observed: 0.279 

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Literature

Highly selective 2,4-diaminopyrimidine-5-carboxamide inhibitors of Sky kinase.

Powell, N.A., Hoffman, J.K., Ciske, F.L., Kaufman, M.D., Kohrt, J.T., Quin, J., Sheehan, D.J., Delaney, A., Baxi, S.M., Catana, C., McConnell, P., Ohren, J., Perrin, L.A., Edmunds, J.J.

(2013) Bioorg Med Chem Lett 23: 1046-1050

  • DOI: https://doi.org/10.1016/j.bmcl.2012.12.013
  • Primary Citation of Related Structures:  
    4FEQ, 4FF8

  • PubMed Abstract: 

    We report the SAR around a series of 2,4-diaminopyrimidine-5-carboxamide inhibitors of Sky kinase. 2-Aminophenethyl analogs demonstrate excellent potency but moderate kinase selectivity, while 2-aminobenzyl analogs that fill the Ala571 subpocket exhibit good inhibition activity and excellent kinase selectivity.

    • Organizational Affiliation: 

    Pfizer Global Research & Development, Michigan Laboratories, Ann Arbor, MI 48105, USA. napowell@comcast.net


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase receptor TYRO3323Mus musculusMutation(s): 0 
Gene Names: Tyro3, Dtk, Rse
EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for P55144 (Mus musculus)
Explore P55144 
Go to UniProtKB:  P55144
IMPC:  MGI:104294
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP55144
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
14S
Query on 14S
Download Ideal Coordinates CCD File 
B [auth A]4-(cyclopentylamino)-2-[(2-methoxybenzyl)amino]-N-[3-(2-oxopyrrolidin-1-yl)propyl]pyrimidine-5-carboxamide
C25 H34 N6 O3
ZXZLVQGNVOKCAS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
14S PDBBind:  4FF8 IC50: 400 (nM) from 1 assay(s)
BindingDB:  4FF8 IC50: 400 (nM) from 1 assay(s)
Binding MOAD:  4FF8 IC50: 400 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.324 
  • R-Value Work: 0.277 
  • R-Value Observed: 0.279 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.522α = 90
b = 57.245β = 100.85
c = 60.076γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
REFMACphasing

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: 2013-03-13
    Type: Initial release
  • Version 1.1: 2024-02-28
    Changes: Data collection, Database references, Derived calculations