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PDBsum entry 3lpb
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Contents |
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* Residue conservation analysis
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PDB id:
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Transferase
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Title:
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Crystal structure of jak2 complexed with a potent 2,8-diaryl- quinoxaline inhibitor
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Structure:
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Tyrosine-protein kinase jak2. Chain: a, b. Fragment: kinase domain. Synonym: janus kinase 2, jak-2. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9de.
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Resolution:
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2.00Å
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R-factor:
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0.178
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R-free:
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0.207
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Authors:
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G.A.Tavares,C.Pissot-Soldermann,M.Gerspacher,P.Furet,M.Kroemer
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Key ref:
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C.Pissot-Soldermann
et al.
(2010).
Discovery and SAR of potent, orally available 2,8-diaryl-quinoxalines as a new class of JAK2 inhibitors.
Bioorg Med Chem Lett,
20,
2609-2613.
PubMed id:
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Date:
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05-Feb-10
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Release date:
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28-Apr-10
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PROCHECK
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Headers
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References
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O60674
(JAK2_HUMAN) -
Tyrosine-protein kinase JAK2 from Homo sapiens
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Seq:
Struc:
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1132 a.a.
280 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.2.7.10.2
- 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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Bioorg Med Chem Lett
20:2609-2613
(2010)
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PubMed id:
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Discovery and SAR of potent, orally available 2,8-diaryl-quinoxalines as a new class of JAK2 inhibitors.
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C.Pissot-Soldermann,
M.Gerspacher,
P.Furet,
C.Gaul,
P.Holzer,
C.McCarthy,
T.Radimerski,
C.H.Regnier,
F.Baffert,
P.Drueckes,
G.A.Tavares,
E.Vangrevelinghe,
F.Blasco,
G.Ottaviani,
F.Ossola,
J.Scesa,
J.Reetz.
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ABSTRACT
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We have designed and synthesized a novel series of 2,8-diaryl-quinoxalines as
Janus kinase 2 inhibitors. Many of the inhibitors show low nanomolar activity
against JAK2 and potently suppress proliferation of SET-2 cells in vitro. In
addition, compounds from this series have favorable rat pharmacokinetic
properties suitable for in vivo efficacy evaluation.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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T.Wang,
S.Ioannidis,
L.Almeida,
M.H.Block,
A.M.Davies,
M.L.Lamb,
D.A.Scott,
M.Su,
H.J.Zhang,
M.Alimzhanov,
G.Bebernitz,
K.Bell,
and
M.Zinda
(2011).
In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors.
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Bioorg Med Chem Lett,
21,
2958-2961.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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Links
