1zom: Difference between revisions

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==Overview==

Human coagulation factor XIa (FXIa), a serine protease activated by, site-specific cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a critical enzyme in the amplification phase of the coagulation, cascade. To investigate the potential of FXIa inhibitors as safe, anticoagulants, a series of potent, selective peptidomimetic inhibitors of, FXIa were designed and synthesized. Some of these inhibitors showed low, nanomolar FXIa inhibitory activity with >1000-fold FXa selectivity and, >100-fold thrombin selectivity. The X-ray structure of one of these, inhibitors, 36, demonstrates its unique binding interactions with FXIa., Compound 32 caused a doubling of the activated partial thromboplastin time, in human plasma at 2.4 microM and was efficacious in a rat model of venous, thrombosis. These data suggest that factor XIa plays a significant role in, venous thrombosis and may be a suitable target for the development of, antithrombotic therapy.

Human coagulation factor XIa (FXIa), a serine protease activated by site-specific cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a critical enzyme in the amplification phase of the coagulation cascade. To investigate the potential of FXIa inhibitors as safe anticoagulants, a series of potent, selective peptidomimetic inhibitors of FXIa were designed and synthesized. Some of these inhibitors showed low nanomolar FXIa inhibitory activity with >1000-fold FXa selectivity and >100-fold thrombin selectivity. The X-ray structure of one of these inhibitors, 36, demonstrates its unique binding interactions with FXIa. Compound 32 caused a doubling of the activated partial thromboplastin time in human plasma at 2.4 microM and was efficacious in a rat model of venous thrombosis. These data suggest that factor XIa plays a significant role in venous thrombosis and may be a suitable target for the development of antithrombotic therapy.

==Disease==

Known diseases associated with this structure: Factor XI deficiency, autosomal dominant OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=264900 264900]], Factor XI deficiency, autosomal recessive OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=264900 264900]]

==About this Structure==

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[[Category: inhibitor]]

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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:17:36 2008''

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@@ Line 4: / Line 4: @@
 ==Overview==
-Human coagulation factor XIa (FXIa), a serine protease activated by, site-specific cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a critical enzyme in the amplification phase of the coagulation, cascade. To investigate the potential of FXIa inhibitors as safe, anticoagulants, a series of potent, selective peptidomimetic inhibitors of, FXIa were designed and synthesized. Some of these inhibitors showed low, nanomolar FXIa inhibitory activity with &gt;1000-fold FXa selectivity and, &gt;100-fold thrombin selectivity. The X-ray structure of one of these, inhibitors, 36, demonstrates its unique binding interactions with FXIa., Compound 32 caused a doubling of the activated partial thromboplastin time, in human plasma at 2.4 microM and was efficacious in a rat model of venous, thrombosis. These data suggest that factor XIa plays a significant role in, venous thrombosis and may be a suitable target for the development of, antithrombotic therapy.
+Human coagulation factor XIa (FXIa), a serine protease activated by site-specific cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a critical enzyme in the amplification phase of the coagulation cascade. To investigate the potential of FXIa inhibitors as safe anticoagulants, a series of potent, selective peptidomimetic inhibitors of FXIa were designed and synthesized. Some of these inhibitors showed low nanomolar FXIa inhibitory activity with &gt;1000-fold FXa selectivity and &gt;100-fold thrombin selectivity. The X-ray structure of one of these inhibitors, 36, demonstrates its unique binding interactions with FXIa. Compound 32 caused a doubling of the activated partial thromboplastin time in human plasma at 2.4 microM and was efficacious in a rat model of venous thrombosis. These data suggest that factor XIa plays a significant role in venous thrombosis and may be a suitable target for the development of antithrombotic therapy.
+==Disease==
+Known diseases associated with this structure: Factor XI deficiency, autosomal dominant OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=264900 264900]], Factor XI deficiency, autosomal recessive OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=264900 264900]]
 ==About this Structure==
@@ Line 29: / Line 32: @@
 [[Category: inhibitor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:29:48 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:17:36 2008''