Figure 2
Figure 2. Relative potencies of polyP inhibitors. (A) Inhibitor concentrations resulting in 50% reduction of thrombin binding to immobilized polyP (IC50) are plotted for the 21 most potent substances tested, expressed in terms of mass (left) and molarity (right). Inhibitors that were also used in panels B and C are numbered in parentheses. Data are mean ± SE (n = 3). (B) Plot of IC50 values of the 11 numbered substances from panel A for inhibition of heparin-mediated inactivation of factor Xa by antithrombin (y-axis) versus inhibition of thrombin binding to immobilized polyP (x-axis). Dotted line represents equivalent potency. Data are mean ± bidirectional SE (although error bars are within the symbols; n = 3). (C) Effectiveness of polyP inhibitors in prolonging clotting. Clotting of human plasma was initiated by long-chain polyP (P), polyguanylic acid (RNA), kaolin (K), diatomaceous earth (Dia), or tissue factor (TF). Data are mean inhibitor concentrations that doubled the clotting time relative to no inhibitor (ECdouble) ± SE (n = 4). Horizontal dotted lines indicate that the clotting time with that initiator was either unaffected by the inhibitor or was not prolonged sufficiently to reach a doubling point, even at 100 μg/mL inhibitor.

Relative potencies of polyP inhibitors. (A) Inhibitor concentrations resulting in 50% reduction of thrombin binding to immobilized polyP (IC50) are plotted for the 21 most potent substances tested, expressed in terms of mass (left) and molarity (right). Inhibitors that were also used in panels B and C are numbered in parentheses. Data are mean ± SE (n = 3). (B) Plot of IC50 values of the 11 numbered substances from panel A for inhibition of heparin-mediated inactivation of factor Xa by antithrombin (y-axis) versus inhibition of thrombin binding to immobilized polyP (x-axis). Dotted line represents equivalent potency. Data are mean ± bidirectional SE (although error bars are within the symbols; n = 3). (C) Effectiveness of polyP inhibitors in prolonging clotting. Clotting of human plasma was initiated by long-chain polyP (P), polyguanylic acid (RNA), kaolin (K), diatomaceous earth (Dia), or tissue factor (TF). Data are mean inhibitor concentrations that doubled the clotting time relative to no inhibitor (ECdouble) ± SE (n = 4). Horizontal dotted lines indicate that the clotting time with that initiator was either unaffected by the inhibitor or was not prolonged sufficiently to reach a doubling point, even at 100 μg/mL inhibitor.

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