› 6tpf

X-ray diffraction
2.31Å resolution

Fragment-based discovery of pyrazolopyridones as JAK1 inhibitors with excellent subtype selectivity

Released:
DOI: 10.2210/pdb6tpf/pdb
PDB entry 6tpf coloured by chain, front view.
PDB entry 6tpf coloured by chain, side view.
PDB entry 6tpf coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Fragment-Based Discovery of Pyrazolopyridones as JAK1 Inhibitors with Excellent Subtype Selectivity.
Hansen BB, Jepsen TH, Larsen M, Sindet R, Vifian T, Burhardt MN, Larsen J, Seitzberg JG, Carnerup MA, Jerre A, Mølck C, Lovato P, Rai S, Nasipireddy VR, Ritzén A
J Med Chem 63 7008-7032 (2020)
PMID: 32462873

Function and Biology Details

Reaction catalysed: 
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-149968 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Tyrosine-protein kinase JAK1 Chains: A, B
Molecule details ›
Chains: A, B
Length: 291 amino acids
Theoretical weight: 33.62 KDa
Source organism: Homo sapiens
Expression system: Not provided
UniProt:
  • Canonical: P23458 (Residues: 864-1154; Coverage: 25%)
Gene names: JAK1, JAK1A, JAK1B
Sequence domains: Protein tyrosine and serine/threonine kinase

Ligands and Environments

1 bound ligand:
Ligand NTQ 2 x NTQ
1 modified residue:
Ligand PTR 4 x PTR

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: P21
Unit cell:
a: 42.728Å b: 171.198Å c: 44.33Å
α: 90° β: 91.84° γ: 90°
R-values:
R R work R free
0.266 0.263 0.327
Expression system: Not provided

Quick links

Citations

3 review citations

Fragment-to-Lead Medicinal Chemistry Publications in 2020.
de Esch et al. (2022)
2 more

1 mention without citation

Discovery of novel JAK1 inhibitors through combining machine learning, structure-based pharmacophore modeling and bio-evaluation.
Wang et al. (2023)