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PDBsum entry 4xj0
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Transferase/transferase inhibitor
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PDB id
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4xj0
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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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Crystal structure of erk2 in complex with an inhibitor 14k
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Structure:
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Mitogen-activated protein kinase 1. Chain: a, b. Fragment: residues 12-360. Synonym: mapk 1,ert1,extracellular signal-regulated kinase 2,erk-2, map kinase isoform p42,p42-mapk,mitogen-activated protein kinase 2, mapk 2. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk1, erk2, prkm1, prkm2. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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2.58Å
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R-factor:
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0.210
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R-free:
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0.244
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Authors:
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J.Yin,W.Wang
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Key ref:
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L.Ren
et al.
(2015).
Discovery of highly potent, selective, and efficacious small molecule inhibitors of ERK1/2.
J Med Chem,
58,
1976-1991.
PubMed id:
DOI:
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Date:
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08-Jan-15
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Release date:
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16-Sep-15
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PROCHECK
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Headers
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References
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P28482
(MK01_HUMAN) -
Mitogen-activated protein kinase 1 from Homo sapiens
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Seq:
Struc:
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360 a.a.
346 a.a.*
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Key: |
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Secondary structure |
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CATH domain |
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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.2.7.11.24
- mitogen-activated protein kinase.
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Reaction:
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1.
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L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
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2.
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L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H+
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L-seryl-[protein]
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+
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ATP
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=
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O-phospho-L-seryl-[protein]
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+
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ADP
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+
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H(+)
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L-threonyl-[protein]
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+
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ATP
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=
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O-phospho-L-threonyl-[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
58:1976-1991
(2015)
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PubMed id:
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Discovery of highly potent, selective, and efficacious small molecule inhibitors of ERK1/2.
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L.Ren,
J.Grina,
D.Moreno,
J.F.Blake,
J.J.Gaudino,
R.Garrey,
A.T.Metcalf,
M.Burkard,
M.Martinson,
K.Rasor,
H.Chen,
B.Dean,
S.E.Gould,
P.Pacheco,
S.Shahidi-Latham,
J.Yin,
K.West,
W.Wang,
J.G.Moffat,
J.B.Schwarz.
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ABSTRACT
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Using structure-based design, a novel series of pyridone ERK1/2 inhibitors was
developed. Optimization led to the identification of (S)-14k, a potent,
selective, and orally bioavailable agent that inhibited tumor growth in mouse
xenograft models. On the basis of its in vivo efficacy and preliminary safety
profiles, (S)-14k was selected for further preclinical evaluation.
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Links
