› 4ymj

X-ray diffraction
2Å resolution

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

Released:
DOI: 10.2210/pdb4ymj/pdb
PDB entry 4ymj coloured by chain, front view.
PDB entry 4ymj coloured by chain, side view.
PDB entry 4ymj 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-172460 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
NT-3 growth factor receptor Chains: A, B
Molecule details ›
Chains: A, B
Length: 304 amino acids
Theoretical weight: 34.73 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: Q16288 (Residues: 530-839; Coverage: 37%)
Gene names: NTRK3, TRKC
Sequence domains: Protein tyrosine and serine/threonine kinase
Structure domains:

Ligands and Environments

3 bound ligands:
Ligand 4EJ 2 x 4EJ
Ligand GOL 6 x GOL
Ligand CL 1 x CL
1 modified residue:
Ligand SEP 2 x SEP

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.3
Spacegroup: P32
Unit cell:
a: 65.61Å b: 65.61Å c: 175.622Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.166 0.165 0.199
Expression system: Spodoptera frugiperda

Quick links

Citations

7 review citations

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

3 mentions without citation

What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC).
Drilon et al. (2016)
2 more