4ALV: Benzofuropyrimidinone Inhibitors Of Pim-1

A series of substituted benzofuropyrimidinones with pan-PIM activities and excellent selectivity against a panel of diverse kinases is described. Initial exploration identified aryl benzofuropyrimidinones that were potent, but had cell permeability limitation. Using X-ray crystal structures of the bound PIM-1 complexes with 3, 5m, and 6d, we were able to guide the SAR and identify the alkyl benzofuropyrimidinone (6l) with good PIM potencies, permeability, and oral exposure.
PDB ID: 4ALVDownload
MMDB ID: 106654
PDB Deposition Date: 2012/3/5
Updated in MMDB: 2013/01
Experimental Method:
x-ray diffraction
Resolution: 2.59  Å
Source Organism:
Similar Structures:
Biological Unit for 4ALV: monomeric; determined by author and by software (PISA)
Molecular Components in 4ALV
Label Count Molecule
Protein (1 molecule)
Serine/threonine-protein Kinase Pim-1(Gene symbol: PIM1)
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB