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PDBsum entry 3ig6
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Contents |
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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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Low molecular weigth human urokinase type plasminogen activator 2-[6- (3'-aminomethyl-biphenyl-3-yloxy)-4-(3-dimethylamino-pyrrolidin-1- yl)-3,5-difluoro-pyridin-2-yloxy]-4-dimethylamino-benzoic acid complex
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Structure:
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Urokinase-type plasminogen activator. Chain: a, c. Fragment: fragment of light chain. Synonym: u-plasminogen activator, upa, urokinase-type plasminogen activator long chain a, urokinase-type plasminogen activator short chain a, urokinase-type plasminogen activator chain b. Engineered: yes. Urokinase-type plasminogen activator. Chain: b, d.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: plau. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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1.83Å
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R-factor:
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0.198
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R-free:
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0.228
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Authors:
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M.Adler,M.Whitlow
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Key ref:
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C.W.West
et al.
(2009).
Identification of orally bioavailable, non-amidine inhibitors of Urokinase Plasminogen Activator (uPA).
Bioorg Med Chem Lett,
19,
5712-5715.
PubMed id:
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Date:
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27-Jul-09
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Release date:
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13-Oct-09
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PROCHECK
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Headers
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References
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P00749
(UROK_HUMAN) -
Urokinase-type plasminogen activator from Homo sapiens
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Seq:
Struc:
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431 a.a.
245 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.3.4.21.73
- u-plasminogen activator.
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Reaction:
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Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.
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Bioorg Med Chem Lett
19:5712-5715
(2009)
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PubMed id:
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Identification of orally bioavailable, non-amidine inhibitors of Urokinase Plasminogen Activator (uPA).
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C.W.West,
M.Adler,
D.Arnaiz,
D.Chen,
K.Chu,
G.Gualtieri,
E.Ho,
C.Huwe,
D.Light,
G.Phillips,
R.Pulk,
D.Sukovich,
M.Whitlow,
S.Yuan,
J.Bryant.
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ABSTRACT
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In this Letter we report the synthesis and evaluation of a series of non-amidine
inhibitors of Urokinase Plasminogen Activator (uPA). Starting from compound 1, a
significant change provided compounds in which the amidine, binding in the S1
pocket, was replaced with a primary amine. Further modifications led to the
identification of potent, selective, and orally bioavailable uPA inhibitors.
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Links
