Structure-Based Design of Macrocyclic Coagulation Factor VIIa Inhibitors
نویسندگان
چکیده
منابع مشابه
Inhibitors of Factor VIIa/tissue factor.
The formation of the proteolytic complex composed of the serine protease Factor VIIa and the cell-associated glycoprotein tissue factor (FVIIa/TF) initiates a cascade of amplified zymogen activation reactions leading to thrombus formation. The critical role of the coagulation cascade in pathological thrombosis has been the basis for significant efforts to design selective inhibitors of the prot...
متن کاملCoagulation and Transfusion Medicine / RECOMBINANT FACTOR VIIA
Recombinant factor VIIa (rFVIIa) has become available for treating people with hemophilia with inhibitors who experience bleeding or require surgery. It has become apparent that rFVIIa is useful in controlling bleeding in a variety of clinical situations. This review attempts to collate and summarize the nonhemophilia applications of rFVIIa. The theoretical mechanism for the coagulation and hem...
متن کاملStructural biology of factor VIIa/tissue factor initiated coagulation.
Factor VII (FVII) consists of an N-terminal gamma-carboxyglutamic acid domain followed by two epidermal growth factor-like (EGF1 and EGF2) domains and the C-terminal protease domain. Activation of FVII results in a two-chain FVIIa molecule consisting of a light chain (Gla-EGF1-EGF2 domains) and a heavy chain (protease domain) held together by a single disulfide bond. During coagulation, the com...
متن کاملThe quest for Factor VIIa exosite inhibitors.
Coagulation proteases are involved in a highly orchestrated proteolytic cascade which is essential for haemostasis and blood clotting. In particular, the initiator of the coagulation cascade, Factor VIIa, binds to its cofactor, tissue factor, and its substrate, Factor X, via exosite interactions to form a ternary catalytic complex named extrinsic Xase. These exosite interactions have also been ...
متن کاملStructure of human factor VIIa and its implications for the triggering of blood coagulation.
Factor VIIa (EC 3.4.21.21) is a trypsin-like serine protease that plays a key role in the blood coagulation cascade. On injury, factor VIIa forms a complex with its allosteric regulator, tissue factor, and initiates blood clotting. Although the structure of the binary complex has already been determined [Banner, D. W., D'Arcy, A., Chène, C., Winkler, F. K., Guha, A., Konigsberg, W. H., Nemerson...
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ژورنال
عنوان ژورنال: Journal of Medicinal Chemistry
سال: 2015
ISSN: 0022-2623,1520-4804
DOI: 10.1021/acs.jmedchem.5b00788