Shifting Paradigms: Examining
Pro-Thrombotic Activity from a
Safety Perspective
CorDynamics conducts thrombosis experiments – using small and
large animals
Mouse ferric chloride model of arterial thromb...
Effects of various concentrations FeCl3 on carotid artery blood flow
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Reducing FeCl3 reduces thrombosis – prothrombotic window opens
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Shifting Paradigms: Examining Pro-Thrombotic Activity from a Safety Perspective

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This research marks the evolution of anti-thrombosis discovery investigations into pro-thrombotic safety models. Clearly, pro-thrombotic activity is an undesirable property for drugs outside the cardiovascular arena. The ability to create a pro-thrombotic window provides safety intel on lead candidates.

Published in: Health & Medicine
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Shifting Paradigms: Examining Pro-Thrombotic Activity from a Safety Perspective

  1. 1. Shifting Paradigms: Examining Pro-Thrombotic Activity from a Safety Perspective
  2. 2. CorDynamics conducts thrombosis experiments – using small and large animals Mouse ferric chloride model of arterial thrombosis 1) instrumentation to monitor carotid artery flow - monitor artery flow prior to and after FeCl3 - FeCl3 migrates to lumen, results in endothelial injury 2) administer test article prior to FeCl3 -monitor for development of thrombus -use real-time monitor of blood flow, time to occlusion Validation - reduced concentrations of FeCl3, vessel vulnerability present
  3. 3. Effects of various concentrations FeCl3 on carotid artery blood flow 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 -1 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 59 61 mL/min Time (minutes) Concetration-dependent effects of Ferric Chloride on Carotid Arterial Thrombosis in CD-1 Mice Carotid Artery Flow Vehicle (PBS, 3.5% FeCl3- Lot SZBE1900V) (n=5) Vehicle (PBS, 3.0% FeCl3- Lot SZBE1900V) (n=10) Vehicle (PBS, 2.8% FeCl3- Lot SZBE1900V) (n=10) Vehicle (PBS, 2.5% FeCl3- Lot SZBE1900V) (n=10) FeCl3
  4. 4. Reducing FeCl3 reduces thrombosis – prothrombotic window opens 0 5 10 15 20 25 30 35 40 45 50 55 60 0 10 20 30 40 50 60 70 80 90 100 3.5% FeCl3 Lot SZBE1900V 3.0% FeCl3 Lot SZBE1900V 2.8% FeCl3 Lot SZBE1900V 2.5% FeCl3 Lot SZBE1900V ProThrombotic OcclusionTime(min) Incidenceofnon–Occlusion(%) Concetration-dependent effects of Ferric Chloride on Carotid Arterial Thrombosis in CD-1 Mice Occlusion time Incidence of non-occlusion 4/10 1 out of 1 1 out of 1 2/10 6/10 0/7 ?

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