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PDBsum entry 5fdp
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PDB id:
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Transferase
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Title:
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Structure of ddr1 receptor tyrosine kinase in complex with d2099 inhibitor at 2.25 angstroms resolution.
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Structure:
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Epithelial discoidin domain-containing receptor 1. Chain: a. Fragment: unp residues 601-903. Synonym: epithelial discoidin domain receptor 1,cd167 antigen-like family member a,cell adhesion kinase,discoidin receptor tyrosine kinase,hgk2,mammary carcinoma kinase 10,mck-10,protein-tyrosine kinase 3a,protein-tyrosine kinase rtk-6,trk e,tyrosine kinase ddr, tyrosine-protein kinase cak. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: ddr1, cak, eddr1, nep, ntrk4, ptk3a, rtk6, trke. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108
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Resolution:
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2.25Å
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R-factor:
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0.191
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R-free:
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0.269
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Authors:
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S.G.Bartual,D.M.Pinkas,Z.Wang,K.Ding,P.Mahajan,K.Kupinska, S.Mukhopadhyay,C.Strain-Damerell,O.Borkowska,R.Talon,J.Kopec, E.Williams,C.Tallant,A.Chaikuad,F.Sorell,J.Newman,N.Burgess-Brown, C.H.Arrowsmith,F.Von Delft,A.M.Edwards,C.Bountra,A.Bullock, Structural Genomics Consortium (Sgc)
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Key ref:
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Z.Wang
et al.
(2016).
Structure-Based Design of Tetrahydroisoquinoline-7-carboxamides as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors.
J Med Chem,
59,
5911-5916.
PubMed id:
DOI:
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Date:
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16-Dec-15
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Release date:
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08-Jun-16
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PROCHECK
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Headers
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References
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Q08345
(DDR1_HUMAN) -
Epithelial discoidin domain-containing receptor 1 from Homo sapiens
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Seq:
Struc:
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913 a.a.
285 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.2.7.10.1
- receptor protein-tyrosine kinase.
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Reaction:
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L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
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L-tyrosyl-[protein]
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+
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ATP
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=
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O-phospho-L-tyrosyl-[protein]
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+
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ADP
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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J Med Chem
59:5911-5916
(2016)
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PubMed id:
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Structure-Based Design of Tetrahydroisoquinoline-7-carboxamides as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors.
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Z.Wang,
H.Bian,
S.G.Bartual,
W.Du,
J.Luo,
H.Zhao,
S.Zhang,
C.Mo,
Y.Zhou,
Y.Xu,
Z.Tu,
X.Ren,
X.Lu,
R.A.Brekken,
L.Yao,
A.N.Bullock,
J.Su,
K.Ding.
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ABSTRACT
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The structure-based design of 1, 2, 3, 4-tetrahydroisoquinoline derivatives as
selective DDR1 inhibitors is reported. One of the representative compounds, 6j,
binds to DDR1 with a Kd value of 4.7 nM and suppresses its kinase activity with
an IC50 value of 9.4 nM, but it is significantly less potent for a panel of 400
nonmutated kinases. 6j also demonstrated reasonable pharmacokinetic properties
and a promising oral therapeutic effect in a bleomycin-induced mouse pulmonary
fibrosis model.
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