Identifying new clotting factor XIa inhibitors in virtual high‐throughput screens using PCA‐GA‐SVM models and signature

Blood Clotting Factor XI is an important actor in the clotting mechanism: it activates downstream zymogen involved in the clotting process. It can be targeted for activation or inhibition depending on treatment goals to enhance or inhibit clotting. In terms of antithrombosis treatment, Factor XI has...

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Bibliographic Details
Published in:Biotechnology progress 2018-11, Vol.34 (6), p.1553-1565
Main Authors: Chen, Jonathan J., Schmucker, Lyndsey N., Visco, Donald P.
Format: Article
Language:English
Subjects:
Blood coagulation
Clotting
Coagulation factors
data mining
drug discovery
Factor XIa
Inhibitors
Iterative methods
Organic chemistry
Proenzymes
QSAR
Signature
virtual high‐throughput screening
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Summary:Blood Clotting Factor XI is an important actor in the clotting mechanism: it activates downstream zymogen involved in the clotting process. It can be targeted for activation or inhibition depending on treatment goals to enhance or inhibit clotting. In terms of antithrombosis treatment, Factor XI has emerged as a promising target to focus on. In this work, an iterative virtual high‐throughput screening pipeline was proposed that can supplement current efforts to find inhibitors. The first iteration identified 11 compounds to test with 3 active for a hit‐rate of 27.3%. The second iteration of the pipeline identified another 11 compounds to test with 7 active for a hit‐rate of 63.6%. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1553–1565, 2018
ISSN:8756-7938
1520-6033
DOI:10.1002/btpr.2693