› 5dwr

X-ray diffraction
2Å resolution

Identification of N-(4-((1R,3S,5S)-3-amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide (PIM447), a Potent and Selective Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1,2 and 3 Kinase Inhibitor in Clinical Trials for Hematological Malignancies

Released:
DOI: 10.2210/pdb5dwr/pdb
PDB entry 5dwr coloured by chain, front view.
PDB entry 5dwr coloured by chain, side view.
PDB entry 5dwr coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Identification of N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide (PIM447), a Potent and Selective Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1, 2, and 3 Kinase Inhibitor in Clinical Trials for Hematological Malignancies.
Burger MT, Nishiguchi G, Han W, Lan J, Simmons R, Atallah G, Ding Y, Tamez V, Zhang Y, Mathur M, Muller K, Bellamacina C, Lindvall MK, Zang R, Huh K, Feucht P, Zavorotinskaya T, Dai Y, Basham S, Chan J, Ginn E, Aycinena A, Holash J, Castillo J, Langowski JL, Wang Y, Chen MY, Lambert A, Fritsch C, Kauffmann A, Pfister E, Vanasse KG, Garcia PD
J Med Chem 58 8373-86 (2015)
PMID: 26505898

Function and Biology Details

Reaction catalysed: 
ATP + a protein = ADP + a phosphoprotein
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-145753 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Serine/threonine-protein kinase pim-1 Chain: A
Molecule details ›
Chain: A
Length: 328 amino acids
Theoretical weight: 37.6 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P11309 (Residues: 2-313; Coverage: 100%)
Gene name: PIM1
Sequence domains: Protein kinase domain
Structure domains:

Ligands and Environments

1 bound ligand:
Ligand 5H7 1 x 5H7
1 modified residue:
Ligand SEP 1 x SEP

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.1
Spacegroup: P65
Unit cell:
a: 98.233Å b: 98.233Å c: 81.123Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.175 0.173 0.202
Expression system: Escherichia coli

Quick links

Citations

4 review citations

Multiple myeloma in the marrow: pathogenesis and treatments.
Fairfield et al. (2016)
3 more

6 mentions without citation

Chemical space exploration based on recurrent neural networks: applications in discovering kinase inhibitors.
Li et al. (2020)
5 more