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Blood clotting
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PDB id
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2b7d
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Contents |
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94 a.a.
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254 a.a.
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149 a.a.
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* Residue conservation analysis
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PDB id:
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| Name: |
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Blood clotting
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Title:
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Factor viia inhibitors: chemical optimization, preclinical pharmacokinetics, pharmacodynamics, and efficacy in a baboon thrombosis model
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Structure:
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Coagulation factor vii. Chain: l. Fragment: light chain. Synonym: serum prothrombin conversion accelerator, spca, proconvertin, eptacog alfa. Engineered: yes. Coagulation factor vii. Chain: h. Fragment: heavy chain.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: f7. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek 293. Expression_system_atcc_number: crl-1573. Gene: f3.
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Biol. unit:
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Trimer (from
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Resolution:
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2.24Å
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R-factor:
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0.247
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R-free:
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0.289
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Authors:
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W.B.Young,J.Mordenti,S.Torkelson,W.D.Shrader,A.Kolesnikov, R.Rai,L.Liu,H.Hu,E.M.Leahy,M.J.Green,P.A.Sprengeler, B.A.Katz,C.Yu,J.W.Janc,K.C.Elrod,U.M.Marzec,S.R.Hanson
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Key ref:
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W.B.Young
et al.
(2006).
Factor VIIa inhibitors: chemical optimization, preclinical pharmacokinetics, pharmacodynamics, and efficacy in an arterial baboon thrombosis model.
Bioorg Med Chem Lett,
16,
2037-2041.
PubMed id:
DOI:
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Date:
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04-Oct-05
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Release date:
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14-Feb-06
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PROCHECK
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Headers
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References
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P08709
(FA7_HUMAN) -
Coagulation factor VII
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Seq:
Struc:
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466 a.a.
94 a.a.
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Enzyme class:
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Chains L, H:
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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Gene Ontology (GO) functional annotation
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Cellular component
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extracellular region
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2 terms
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Biological process
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blood coagulation
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2 terms
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Biochemical function
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catalytic activity
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4 terms
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DOI no:
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Bioorg Med Chem Lett
16:2037-2041
(2006)
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PubMed id:
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Factor VIIa inhibitors: chemical optimization, preclinical pharmacokinetics, pharmacodynamics, and efficacy in an arterial baboon thrombosis model.
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W.B.Young,
J.Mordenti,
S.Torkelson,
W.D.Shrader,
A.Kolesnikov,
R.Rai,
L.Liu,
H.Hu,
E.M.Leahy,
M.J.Green,
P.A.Sprengeler,
B.A.Katz,
C.Yu,
J.W.Janc,
K.C.Elrod,
U.M.Marzec,
S.R.Hanson.
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ABSTRACT
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Highly selective and potent factor VIIa-tissue factor (fVIIa.TF) complex
inhibitors were generated through structure-based design. The pharmacokinetic
properties of an optimized analog (9) were characterized in several preclinical
species, demonstrating pharmacokinetic characteristics suitable for once-a-day
dosing in humans. Analog 9 inhibited platelet and fibrin deposition in a
dose-dependent manner after intravenous administration in a baboon thrombosis
model, and a pharmacodynamic concentration-response model was developed to
describe the platelet deposition data. Results for heparin and enoxaparin
(Lovenox) in the baboon model are also presented.
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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.Shiraishi,
S.Kadono,
M.Haramura,
H.Kodama,
Y.Ono,
H.Iikura,
T.Esaki,
T.Koga,
K.Hattori,
Y.Watanabe,
A.Sakamoto,
K.Yoshihashi,
T.Kitazawa,
K.Esaki,
M.Ohta,
H.Sato,
and
T.Kozono
(2010).
Design and synthesis of peptidomimetic factor VIIa inhibitors.
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Chem Pharm Bull (Tokyo), 58,
38-44.
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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
