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PDBsum entry 5u6j
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Hydrolase/hydrolase inhibitor
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PDB id
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5u6j
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PDB id:
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| Name: |
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Hydrolase/hydrolase inhibitor
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Title:
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Factor viia in complex with the inhibitor 3-{[(2r)-17-ethyl-4-methyl- 3,12-dioxo-7-[(propan-2-yl)sulfonyl]-13-oxa-4,11- diazatricyclo[14.2.2.1~6,10~]henicosa-1(18),6(21),7,9,16,19-hexaen-2- yl]amino}benzamide
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Structure:
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Coagulation factor vii heavy chain. Chain: h. Synonym: proconvertin,serum prothrombin conversion accelerator,spca. Engineered: yes. Coagulation factor vii light chain. Chain: l. Synonym: proconvertin,serum prothrombin conversion accelerator,spca. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: f7. Expressed in: cricetinae. Expression_system_taxid: 10026. Expression_system_taxid: 10026
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Resolution:
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2.30Å
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R-factor:
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0.189
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R-free:
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0.220
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Authors:
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A.Wei
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Key ref:
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N.R.Wurtz
et al.
(2017).
Neutral macrocyclic factor VIIa inhibitors.
Bioorg Med Chem Lett,
27,
2650-2654.
PubMed id:
DOI:
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Date:
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08-Dec-16
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Release date:
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10-May-17
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PROCHECK
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Headers
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References
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Enzyme class:
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Chains H, L:
E.C.3.4.21.21
- coagulation factor VIIa.
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Reaction:
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Hydrolyzes one Arg-|-Ile bond in factor X to form factor Xa.
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DOI no:
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Bioorg Med Chem Lett
27:2650-2654
(2017)
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PubMed id:
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Neutral macrocyclic factor VIIa inhibitors.
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N.R.Wurtz,
B.L.Parkhurst,
I.DeLucca,
P.W.Glunz,
W.Jiang,
X.Zhang,
D.L.Cheney,
J.M.Bozarth,
A.R.Rendina,
A.Wei,
T.Harper,
J.M.Luettgen,
Y.Wu,
P.C.Wong,
D.A.Seiffert,
R.R.Wexler,
E.S.Priestley.
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ABSTRACT
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Factor VIIa (FVIIa) inhibitors have shown strong antithrombotic efficacy in
preclinical thrombosis models with limited bleeding liabilities. Discovery of
potent, orally active FVIIa inhibitors has been largely unsuccessful due to the
requirement of a basic P1 group to interact with Asp189 in the S1 binding
pocket, limiting their membrane permeability. We have combined recently reported
neutral P1 binding substituents with a highly optimized macrocyclic chemotype to
produce FVIIa inhibitors with low nanomolar potency and enhanced permeability.
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Links
