4RPV

co-crystal structure of Pim1 with compound 3


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.05 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.229 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

The discovery of novel 3-(pyrazin-2-yl)-1H-indazoles as potent pan-Pim kinase inhibitors.

Wang, H.L.Cee, V.J.Chavez, F.Lanman, B.A.Reed, A.B.Wu, B.Guerrero, N.Lipford, J.R.Sastri, C.Winston, J.Andrews, K.L.Huang, X.Lee, M.R.Mohr, C.Xu, Y.Zhou, Y.Tasker, A.S.

(2015) Bioorg Med Chem Lett 25: 834-840

  • DOI: https://doi.org/10.1016/j.bmcl.2014.12.068
  • Primary Citation of Related Structures:  
    4RPV, 4WRS

  • PubMed Abstract: 

    The three Pim kinases are a small family of serine/threonine kinases regulating several signaling pathways that are fundamental to tumorigenesis. As such, the Pim kinases are a very attractive target for pharmacological inhibition in cancer therapy. Herein, we describe our efforts toward the development of a potent, pan-Pim inhibitor. The synthesis and hit-to-lead SAR development from a 3-(pyrazin-2-yl)-1H-indazole derived hit 2 to the identification of a series of potent, pan-Pim inhibitors such as 13o are described.


  • Organizational Affiliation

    Department of Therapeutic Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. Electronic address: huiw@amgen.com.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serine/threonine-protein kinase pim-1410Homo sapiensMutation(s): 0 
Gene Names: PIM1
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for P11309 (Homo sapiens)
Explore P11309 
Go to UniProtKB:  P11309
PHAROS:  P11309
GTEx:  ENSG00000137193 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP11309
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
3UR
Query on 3UR

Download Ideal Coordinates CCD File 
B [auth A](3S)-1-{6-[5-(2,6-difluorophenyl)-2H-indazol-3-yl]pyrazin-2-yl}piperidin-3-amine
C22 H20 F2 N6
HWIDISMNBLRQNP-AWEZNQCLSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.05 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.229 
  • Space Group: P 65
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 100.091α = 90
b = 100.091β = 90
c = 81.205γ = 120
Software Package:
Software NamePurpose
HKL-2000data collection
AMoREphasing
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2015-02-04 
  • Deposition Author(s): Huang, X.

Revision History  (Full details and data files)

  • Version 1.0: 2015-02-04
    Type: Initial release
  • Version 1.1: 2015-02-18
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations