3R00

The discovery of novel benzofuran-2-carboxylic acids as potent Pim-1 inhibitors

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.175 

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Ligand Structure Quality Assessment 


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Literature

The discovery of novel benzofuran-2-carboxylic acids as potent Pim-1 inhibitors.

Xiang, Y., Hirth, B., Asmussen, G., Biemann, H.P., Bishop, K.A., Good, A., Fitzgerald, M., Gladysheva, T., Jain, A., Jancsics, K., Liu, J., Metz, M., Papoulis, A., Skerlj, R., Stepp, J.D., Wei, R.R.

(2011) Bioorg Med Chem Lett 21: 3050-3056

  • DOI: https://doi.org/10.1016/j.bmcl.2011.03.030
  • Primary Citation of Related Structures:  
    3R00, 3R01, 3R02, 3R04

  • PubMed Abstract: 

    Novel benzofuran-2-carboxylic acids, exemplified by 29, 38 and 39, have been discovered as potent Pim-1 inhibitors using fragment based screening followed by X-ray structure guided medicinal chemistry optimization. The compounds demonstrate potent inhibition against Pim-1 and Pim-2 in enzyme assays. Compound 29 has been tested in the Ambit 442 kinase panel and demonstrates good selectivity for the Pim kinase family. X-ray structures of the inhibitor/Pim-1 binding complex reveal important salt-bridge and hydrogen bond interactions mediated by the compound's carboxylic acid and amino groups.

    • Organizational Affiliation: 

    Department of Medicinal Chemistry, Drug and Biomaterial R&D, Genzyme Corp., 153 Second Avenue, Waltham, MA 02451, USA. yibin.xiang@genzyme.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Proto-oncogene serine/threonine-protein kinase pim-1299Homo 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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
UNJ
Query on UNJ
Download Ideal Coordinates CCD File 
C [auth A]5-bromo-1-benzofuran-2-carboxylic acid
C9 H5 Br O3
QKUWZCOVKRUXKX-UHFFFAOYSA-N
IMD
Query on IMD
Download Ideal Coordinates CCD File 
B [auth A]IMIDAZOLE
C3 H5 N2
RAXXELZNTBOGNW-UHFFFAOYSA-O
Binding Affinity Annotations 
IDSourceBinding Affinity
UNJ PDBBind:  3R00 IC50: 8500 (nM) from 1 assay(s)
BindingDB:  3R00 IC50: min: 8500, max: 9000 (nM) from 2 assay(s)
Binding MOAD:  3R00 IC50: 8500 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.175 
  • Space Group: P 65
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 97.652α = 90
b = 97.652β = 90
c = 80.826γ = 120
Software Package:
Software NamePurpose
HKL-2000data collection
MOLREPphasing
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

  • Released Date: 2011-05-11 
    • Deposition Author(s): Liu, J.

Revision History  (Full details and data files)

  • Version 1.0: 2011-05-11
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations