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PDBsum entry 5vgo
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Transferase/transferase inhibitor
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PDB id
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5vgo
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PDB id:
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| Name: |
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Transferase/transferase inhibitor
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Title:
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Bruton's tyrosine kinase (btk) with compound g-744
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Structure:
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Tyrosine-protein kinase btk. Chain: a. Fragment: unp residues 427-691. Synonym: agammaglobulinemia tyrosine kinase,atk,b-cell progenitor kinase,bpk,bruton tyrosine kinase. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: btk, agmx1, atk, bpk. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108
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Resolution:
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1.62Å
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R-factor:
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0.162
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R-free:
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0.184
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Authors:
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C.Yu,C.Eigenbrot
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Key ref:
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X.Wang
et al.
(2017).
Discovery of Potent and Selective Tricyclic Inhibitors of Bruton's Tyrosine Kinase with Improved Druglike Properties.
ACS Med Chem Lett,
8,
608-613.
PubMed id:
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Date:
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11-Apr-17
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Release date:
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05-Jul-17
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PROCHECK
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Headers
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References
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Q06187
(BTK_HUMAN) -
Tyrosine-protein kinase BTK from Homo sapiens
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Seq:
Struc:
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659 a.a.
265 a.a.*
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Key: |
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Secondary structure |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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Enzyme class:
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E.C.2.7.10.2
- non-specific 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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ACS Med Chem Lett
8:608-613
(2017)
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PubMed id:
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Discovery of Potent and Selective Tricyclic Inhibitors of Bruton's Tyrosine Kinase with Improved Druglike Properties.
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X.Wang,
J.Barbosa,
P.Blomgren,
M.C.Bremer,
J.Chen,
J.J.Crawford,
W.Deng,
L.Dong,
C.Eigenbrot,
S.Gallion,
J.Hau,
H.Hu,
A.R.Johnson,
A.Katewa,
J.E.Kropf,
S.H.Lee,
L.Liu,
J.W.Lubach,
J.Macaluso,
P.Maciejewski,
S.A.Mitchell,
D.F.Ortwine,
J.DiPaolo,
K.Reif,
H.Scheerens,
A.Schmitt,
H.Wong,
J.M.Xiong,
J.Xu,
Z.Zhao,
F.Zhou,
K.S.Currie,
W.B.Young.
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ABSTRACT
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In our continued effort to discover and develop best-in-class Bruton's tyrosine
kinase (Btk) inhibitors for the treatment of B-cell lymphomas, rheumatoid
arthritis, and systemic lupus erythematosus, we devised a series of novel
tricyclic compounds that improved upon the druglike properties of our previous
chemical matter. Compounds exemplified byG-744are highly potent,
selective for Btk, metabolically stable, well tolerated, and efficacious in an
animal model of arthritis.
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Links
