› 5j87

X-ray diffraction
1.59Å resolution

Discovery of N-(3-(5-((3-acrylamido-4-(morpholine-4-carbonyl)phenyl)amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-methylphenyl)-4-(tert-butyl)benzamide (CHMFL-BTK-01) as a Highly Selective Irreversible BTK Kinase Inhibitor

Released:
DOI: 10.2210/pdb5j87/pdb
PDB entry 5j87 coloured by chain, front view.
PDB entry 5j87 coloured by chain, side view.
PDB entry 5j87 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of N-(3-(5-((3-acrylamido-4-(morpholine-4-carbonyl)phenyl)amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-methylphenyl)-4-(tert-butyl)benzamide (CHMFL-BTK-01) as a highly selective irreversible Bruton's tyrosine kinase (BTK) inhibitor.
Liang Q, Chen Y, Yu K, Chen C, Zhang S, Wang A, Wang W, Wu H, Liu X, Wang B, Wang L, Hu Z, Wang W, Ren T, Zhang S, Liu Q, Yun CH, Liu J
Eur J Med Chem 131 107-125 (2017)
PMID: 28315597

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:
homo tetramer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-554811 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Tyrosine-protein kinase BTK Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 274 amino acids
Theoretical weight: 31.87 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: Q06187 (Residues: 385-658; Coverage: 42%)
Gene names: AGMX1, ATK, BPK, BTK
Sequence domains: Protein tyrosine and serine/threonine kinase
Structure domains:

Ligands and Environments

1 bound ligand:
Ligand N42 4 x N42
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRF BEAMLINE BL19U1
Spacegroup: P21
Unit cell:
a: 41.761Å b: 93.55Å c: 145.889Å
α: 90° β: 89.94° γ: 90°
R-values:
R R work R free
0.22 0.216 0.248
Expression system: Spodoptera frugiperda

Quick links

Citations

2 review citations

Bleeding by Bruton Tyrosine Kinase-Inhibitors: Dependency on Drug Type and Disease.
von Hundelshausen et al. (2021)
1 more

2 mentions without citation

Target Specific Inhibition of Protein Tyrosine Kinase in Conjunction With Cancer and SARS-COV-2 by Olive Nutraceuticals.
Ghosh et al. (2021)
1 more