Supplementary Materials

Supplementary Material for:

Blockade of protease-activated receptor-4 (PAR4) provides robust antithrombotic activity with low bleeding

Pancras C. Wong,* Dietmar Seiffert, J. Eileen Bird, Carol A. Watson, Jeffrey S. Bostwick, Mary Giancarli, Nick Allegretto, Ji Hua, David Harden, Jocelyne Guay, Mario Callejo, Michael M. Miller, R. Michael Lawrence, Jacques Banville, Julia Guy, Brad D. Maxwell, E. Scott Priestley, Anne Marinier, Ruth R. Wexler, Michel Bouvier, David A. Gordon, William A. Schumacher, Jing Yang

*Corresponding author. Email: pancras.wong{at}bms.com

Published 4 January 2017, Sci. Transl. Med. 9, eaaf5294 (2017)
DOI: 10.1126/scitranslmed.aaf5294

This PDF file includes:

  • Materials and Methods
  • Fig. S1. In vitro characterization of anti-PAR4 antibodies in guinea pig platelet aggregation assays.
  • Fig. S2. High-affinity and reversible binding of BMS-986120 to human PAR4.
  • Fig. S3. Inhibition of PAR4 AP–induced signaling pathways by BMS-986120.
  • Fig. S4. Schematic representation of the clopidogrel study protocol.
  • Fig. S5. Dose-dependent increases in plasma concentration of clopidogrel active metabolite in monkeys.
  • Fig. S6. Ex vivo effects of clopidogrel on platelet aggregation and P2Y12 receptor occupancy in monkeys.
  • Fig. S7. Dose-response effects of clopidogrel active metabolite H4 on thrombus weight in monkeys.
  • Fig. S8. Schematic representation of the BMS-986120 study protocol.
  • Fig. S9. Dose-dependent increases in plasma concentration of BMS-986120 in monkeys.
  • Fig. S10. Dose-response effects of BMS-986120 on thrombus weight in monkeys.
  • Fig. S11. Comparison of dose-dependent effect of clopidogrel and BMS-986120 on integrated blood flow and BTs.
  • Fig. S12. Synthesis of BMS-986120.
  • Fig. S13. Synthesis of [3H]BMS-986120.
  • Table S1. Individual animal data from guinea pig carotid artery injury model.
  • Table S2. Individual animal data from guinea pig bleeding model.
  • Table S3. In vitro selectivity of BMS-986120 in the calcium mobilization assays.
  • Table S4. BMS-986120 specificity against enzymatic activity of coagulation proteases.
  • Table S5. Cynomolgus monkeys in the studies of clopidogrel and BMS-986120.
  • References (5660)

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