› 4yne

X-ray diffraction
2.02Å resolution

(R)-2-Phenylpyrrolidine Substitute Imidazopyridazines: a New Class of Potent and Selective Pan-TRK Inhibitors

Released:
DOI: 10.2210/pdb4yne/pdb
PDB entry 4yne coloured by chain, front view.
PDB entry 4yne coloured by chain, side view.
PDB entry 4yne coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
(R)-2-Phenylpyrrolidine Substituted Imidazopyridazines: A New Class of Potent and Selective Pan-TRK Inhibitors.
Choi HS, Rucker PV, Wang Z, Fan Y, Albaugh P, Chopiuk G, Gessier F, Sun F, Adrian F, Liu G, Hood T, Li N, Jia Y, Che J, McCormack S, Li A, Li J, Steffy A, Culazzo A, Tompkins C, Phung V, Kreusch A, Lu M, Hu B, Chaudhary A, Prashad M, Tuntland T, Liu B, Harris J, Seidel HM, Loren J, Molteni V
ACS Med Chem Lett 6 562-7 (2015)
PMID: 26005534

Function and Biology Details

Reaction catalysed: 
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-138088 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
High affinity nerve growth factor receptor Chain: A
Molecule details ›
Chain: A
Length: 303 amino acids
Theoretical weight: 34.26 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P04629 (Residues: 502-796; Coverage: 39%)
Gene names: MTC, NTRK1, TRK, TRKA
Sequence domains: Protein tyrosine and serine/threonine kinase
Structure domains:

Ligands and Environments

3 bound ligands:
Ligand 4EK 1 x 4EK
Ligand SO4 5 x SO4
Ligand GOL 1 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.3
Spacegroup: R32
Unit cell:
a: 105.747Å b: 105.747Å c: 204.684Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.185 0.183 0.216
Expression system: Spodoptera frugiperda

Quick links

Citations

6 review citations

Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 - Part II.
Bailey et al. (2017)
5 more

4 mentions without citation

Development of small-molecule tropomyosin receptor kinase (TRK) inhibitors for NTRK fusion cancers.
Jiang et al. (2021)
3 more