Results 191 to 200 of about 12,711,395 (233)

Novel Rationally Developed Substrates for Factor IXa Demonstrate Active Site Differentiation between Factor IXa and Factor IXa-Padua

Blood
Background: The goal of achieving therapeutically relevant levels of FIX activity in hemophilia B (HB) has been enhanced with the use of the hyperactive factor IX variant R338L (FIX-Padua). FIX-Padua has between 4 to 9-fold higher specific activity than wild-type (wt-) FIX, although the exact mechanism of enhanced ...
Lei Ke, Lindsey A. George, Nabil K. Thalji   +2 more
openaire   +2 more sources

Phosphatidylserine Regulation of Coagulation Proteins Factor IXa and Factor VIIIa

The Journal of Membrane Biology, 2022
Blood coagulation is an intricate process, and it requires precise control of the activities of pro- and anticoagulant factors and sensitive signaling systems to monitor and respond to blood vessel insults. These requirements are fulfilled by phosphatidylserine, a relatively miniscule-sized lipid molecule amid the myriad of large coagulation proteins ...
Rinku Majumder
openaire   +3 more sources

Discovery of hydroxy pyrimidine Factor IXa inhibitors

Bioorganic & Medicinal Chemistry Letters, 2020
The synthesis and structure activity relationship development of a pyrimidine series of heterocyclic Factor IXa inhibitors is described. Increased selectivity over Factor Xa inhibition was achieved through SAR expansion of the P1 element. Select compounds were evaluated in vivo to assess their plasma levels in rat.
Charles L. Jayne, Teresa Andreani, Tin-Yau Chan, Mariappan V. Chelliah, Martin C. Clasby, Michael Dwyer, Keith A. Eagen, Steve Fried, William J. Greenlee, Zhuyan Guo, Brian Hawes, Alan Hruza, Richard Ingram, Kartik M. Keertikar, Santhosh Neelamkavil, Paul Reichert, Yan Xia, Samuel Chackalamannil   +17 more
openaire   +3 more sources

Antidote-controlled DNA aptamer modulates human factor IXa activity

Bioorganic Chemistry
Thrombosis leads to elevated mortality rates and substantial medical expenses worldwide. Human factor IXa (HFIXa) protease is pivotal in tissue factor (TF)-mediated thrombin generation, and represents a promising target for anticoagulant therapy. We herein isolated novel DNA aptamers that specifically bind to HFIXa through systematic evolution of ...
Liang Fang, Jin Jin, Zhe Zhang, Shuang Yu, Cheng Tian, Fukang Luo, Mengfei Long, Hua Zuo, Shifeng Lou   +8 more
openaire   +3 more sources

Inactivation of factor VIII by factor IXa

Biochemistry, 1992
Factor VIII (FVIII) is the nonproteolytic cofactor for FIXa in the tenase complex of blood coagulation. FVIII is proteolytically activated by thrombin and FXa in vitro to form a heterotrimer with full procoagulant activity. Activated protein C inactivates thrombin-activated FVIII through cleavage adjacent to position Arg 336 in the cofactor.
D P, O'Brien, D, Johnson, P, Byfield, E G, Tuddenham   +3 more
openaire   +2 more sources

An anti‐factor IXa/factor X bispecific antibody, emicizumab, improves ex vivo coagulant potentials in plasma from patients with acquired hemophilia A

Journal of Thrombosis and Haemostasis, 2020
Acquired hemophilia A (AHA) is caused by autoantibodies against factor (F)VIII, and is characterized by severe, spontaneous bleeding, which can be life‐threatening. Emicizumab, an anti‐FIXa/FX bispecific antibody, significantly reduces bleeding events in
M. Takeyama, K. Nogami, Tomoko Matsumoto, Mariko Noguchi-Sasaki, T. Kitazawa, M. Shima   +5 more
semanticscholar   +1 more source

Control Of Factor IXa Production By The Formation Of A Factor XIa-Factor IXa Complex

Thrombosis and Haemostasis, 1981
The activation of factor IX represents a transition step between the “contact phase” and the “phospholipid-dependent phase” of intrinsic blood coagulation. A study was made to see if any of the constituents of either of these phases would influence this activation.
A Jonan, C W Slattery
openaire   +1 more source

SAR and factor IXa crystal structure of a dual inhibitor of factors IXa and Xa

Bioorganic & Medicinal Chemistry Letters, 2004
Modifications to the P4 moiety and pyrazole C3 substituent of factor Xa inhibitor SN-429 provided several new compounds, which are 5-10nM inhibitors of factor IXa. An X-ray crystal structure of one example complexed to factor IXa shows that these compounds adopt a similar binding mode to that previously observed with pyrazole inhibitors in the factor ...
Joanne M, Smallheer, Richard S, Alexander, Jianmin, Wang, Shuaige, Wang, Suanne, Nakajima, Karen A, Rossi, Angela, Smallwood, Frank, Barbera, Debra, Burdick, Joseph M, Luettgen, Robert M, Knabb, Ruth R, Wexler, Prabhakar K, Jadhav   +12 more
openaire   +2 more sources

Factor IXa and Factor X Influence Factor VIIIa Stability and Inactivation Mechanisms In Vitro and In Vivo.

Blood
Deficiency of (f)actor VIII causes hemophilia A and excess FVIII function increases venous thromboembolic risk. The phenotypic consequences of aberrant FVIII function underscore the importance of understanding mechanisms that downregulate (a)ctivated ...
Johnathan J Morris, Nicole A Parsons, Amelia R. Wilhelm, Robert J. Davidson, Lauren K Olenick, Connor T Watson, Andrew R Vanden Heuvel, Lindsey A. George   +7 more
semanticscholar   +1 more source

In Hemophilia Α Plasma Treated with Emicizumab, Factor IXa in Activated Prothrombin Complex Concentrates Is the Dominant Contributor to Enhanced Thrombin Generation

, 2020
Background. Recently a novel bifunctional antibody (emicizumab) that binds both factor IXa and factor X has been used to treat hemophilia A. Emicizumab has proven remarkably effective as a prophylactic treatment for hemophilia A; however there are ...
D. Monroe, M. Ezban, M. Hoffman
semanticscholar   +1 more source