Discovery methods of coagulation-inhibiting drugs

References

• Gómez-Outes A, Suárez-Gea ML, Calvo-Rojas G, et al. Discovery of anticoagulant drugs: a historical perspective. Curr Drug Discov Technol. 2012;9:83–104.
   PubMedGoogle Scholar
• Kirchhof P, Benussi S, Kotecha D, et al. ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Europace. 2016;2016(18):1609–1678.
   Web of Science ®Google Scholar
• Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149:315–352.
   PubMed Web of Science ®Google Scholar
• Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e278S.
   PubMed Web of Science ®Google Scholar
• Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e227S.
   PubMed Web of Science ®Google Scholar
• Qaseem A, Chou R, Humphrey LL, et al. Venous thromboembolism prophylaxis in hospitalized patients: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2011;155:625–632.
   PubMed Web of Science ®Google Scholar
• Yao X, Abraham NS, Sangaralingham LR, et al. Effectiveness and safety of dabigatran, rivaroxaban, and apixaban versus warfarin in nonvalvular atrial fibrillation. J Am Heart Assoc. 2016;5.
   Web of Science ®Google Scholar
• Power A. Stroke in dialysis and chronic kidney disease. Blood Purif. 2013;36:179–183.
   PubMed Web of Science ®Google Scholar
• Jiménez D, De Miguel-Díez J, Guijarro R, et al. Trends in the management and outcomes of acute pulmonary embolism: analysis from the RIETE registry. J Am Coll Cardiol. 2016;67:162–170.
   PubMed Web of Science ®Google Scholar
• Feuring M, van Ryn J. The discovery of dabigatran etexilate for the treatment of venous thrombosis. Expert Opin Drug Discov. 2016;11:717–731.
   PubMed Web of Science ®Google Scholar
• Kubitza D, Perzborn E, Berkowitz SD. The discovery of rivaroxaban: translating preclinical assessments into clinical practice. Front Pharmacol. 2013;4:145.
   PubMed Web of Science ®Google Scholar
• Wong PC, Pinto DJ, Zhang D. Preclinical discovery of apixaban, a direct and orally bioavailable factor Xa inhibitor. J Thromb Thrombolysis. 2011;31:478–492.
   PubMed Web of Science ®Google Scholar
• Pinto DJ, Orwat MJ, Koch S, et al. Discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, BMS-562247), a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa. J Med Chem. 2007;50:5339–5356.
   PubMed Web of Science ®Google Scholar
• Furugohri T, Isobe K, Honda Y, et al. DU-176b, a potent and orally active factor Xa inhibitor: in vitro and in vivo pharmacological profiles. J Thromb Haemost. 2008;6:1542–1549.
   PubMed Web of Science ®Google Scholar
• Partida RA, Giugliano RP. Edoxaban: pharmacological principles, preclinical and early-phase clinical testing. Future Cardiol. 2011;7:459–470.
   PubMedGoogle Scholar
• Preis M, Hirsch J, Kotler A, et al. Factor XI deficiency is associated with lower risk for cardiovascular and venous thromboembolism events. Blood. 2017;129:1210–1215.
   PubMed Web of Science ®Google Scholar
• Gailani D, Bane CE, Gruber A. Factor XI and contact activation as targets for antithrombotic therapy. J Thromb Haemost. 2015;13:1383–1395.
   PubMed Web of Science ®Google Scholar
• Wheeler AP, Gailani D. The intrinsic pathway of coagulation as a target for antithrombotic therapy. Hematol Oncol Clin North Am. 2016;30:1099–1114.
   PubMed Web of Science ®Google Scholar
• Puy C, Tucker EI, Ivanov IS, et al. Platelet-derived short-chain polyphosphates enhance the inactivation of tissue factor pathway inhibitor by activated coagulation factor XI. PLoS One. 2016;11:e0165172.
   PubMed Web of Science ®Google Scholar
• Kaplan AP, Silverberg M. The coagulation-kinin pathway of human plasma. Blood. 1987;70:1–15.
   PubMed Web of Science ®Google Scholar
• Revenko AS, Gao D, Crosby JR, et al. Selective depletion of plasma prekallikrein or coagulation factor XII inhibits thrombosis in mice without increased risk of bleeding. Blood. 2011;118:5302–5311.
   PubMed Web of Science ®Google Scholar
• Weitz JI, Fredenburgh JC. Factors XI and XII as targets for new anticoagulants. Front Med (Lausanne). 2017;4:19.
   PubMed Web of Science ®Google Scholar
• Hassanian SM, Avan A, Ardeshirylajimi A. Inorganic polyphosphate: a key modulator of inflammation. J Thromb Haemost. 2017;15:213–218.
   PubMed Web of Science ®Google Scholar
• Hernandez-Ruiz L, Saez-Benito A, Pujol-Moix N, et al. Platelet inorganic polyphosphate decreases in patients with delta storage pool disease. J Thromb Haemost. 2009;7:361–363.
   PubMed Web of Science ®Google Scholar
• Mann KG, Brummel K, Butenas S. What is all that thrombin for? J Thromb Haemost. 2003;1:1504–1514.
   PubMed Web of Science ®Google Scholar
• Davie EW, Kulman JD. An overview of the structure and function of thrombin. Semin Thromb Hemost. 2006;32:3–15.
   PubMed Web of Science ®Google Scholar
• Lane DA, Olds RR, Thein SL. Antithrombin and its deficiency states. Blood Coagul Fibrinolysis. 1992;3:315–341.
   PubMed Web of Science ®Google Scholar
• DeAnda A Jr, Coutre SE, Moon MR, et al. Pilot study of the efficacy of a thrombin inhibitor for use during cardiopulmonary bypass. Ann Thorac Surg. 1994;58:344–350.
   PubMed Web of Science ®Google Scholar
• Becker RC, Povsic T, Cohen MG, et al. Nucleic acid aptamers as antithrombotic agents: opportunities in extracellular therapeutics. Thromb Haemost. 2010;103:586–595.
   PubMed Web of Science ®Google Scholar
• Mayer G, Rohrbach F, Pötzsch B, et al. Aptamer-based modulation of blood coagulation. Hamostaseologie. 2011;31:258–263.
   PubMed Web of Science ®Google Scholar
• Tasset DM, Kubik MF, Steiner W. Oligonucleotide inhibitors of human thrombin that bind distinct epitopes. J Mol Biol. 1997;272:688–698.
   PubMed Web of Science ®Google Scholar
• Bompiani KM, Monroe DM, Church FC, et al. A high affinity, antidote-controllable prothrombin and thrombin-binding RNA aptamer inhibits thrombin generation and thrombin activity. J Thromb Haemost. 2012;10:870–880.
   PubMed Web of Science ®Google Scholar
• Dyke CK, Steinhubl SR, Kleiman NS, et al. First-in-human experience of an antidote-controlled anticoagulant using RNA aptamer technology: a phase 1a pharmacodynamic evaluation of a drug-antidote pair for the controlled regulation of factor IXa activity. Circulation. 2006;114:2490–2497.
   PubMed Web of Science ®Google Scholar
• Rusconi CP, Scardino E, Layzer J, et al. RNA aptamers as reversible antagonists of coagulation factor IXa. Nature. 2002;419:90–94.
   PubMed Web of Science ®Google Scholar
• Lincoff AM, Mehran R, Povsic TJ, et al. Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): a randomised clinical trial. Lancet. 2016;387:349–356.
   PubMed Web of Science ®Google Scholar
• Povsic TJ, Lawrence MG, Lincoff AM, et al. Pre-existing anti-PEG antibodies are associated with severe immediate allergic reactions to pegnivacogin, a PEGylated aptamer. J Allergy Clin Immunol. 2016;138:1712–1715.
   PubMed Web of Science ®Google Scholar
• Buddai SK, Layzer JM, Lu G, et al. An anticoagulant RNA aptamer that inhibits proteinase-cofactor interactions within prothrombinase. J Biol Chem. 2010;285:5212–5223.
   PubMed Web of Science ®Google Scholar
• Soule EE, Bompiani KM, Woodruff RS, et al. Targeting two coagulation cascade proteases with a bivalent aptamer yields a potent and antidote-controllable anticoagulant. Nucleic Acid Ther. 2016;26:1–9.
   PubMed Web of Science ®Google Scholar
• Woodruff RS, Ivanov I, Verhamme IM, et al. Generation and characterization of aptamers targeting factor XIa. Thromb Res. 2017;156:134–141.
   PubMed Web of Science ®Google Scholar
• Donkor D, Bhakta V, Eltringham-Smith L, et al. Characterization of an aptamer inhibiting coagulation factor XIa identified through in vitro screening of a single-stranded DNA library. Res Pract Thromb Haemost. 2017;1(Suppl.1). PB 819 [abstract]. 385.
   Google Scholar
• Woodruff RS, Xu Y, Layzer J, et al. Inhibiting the intrinsic pathway of coagulation with a factor XII-targeting RNA aptamer. J Thromb Haemost. 2013;11:1364–1373.
   PubMed Web of Science ®Google Scholar
• Steen-Burrell KA, Layzer J, Sullenger BA. A kallikrein-targeting RNA aptamer inhibits the intrinsic pathway of coagulation and reduces bradykinin release. J Thromb Haemost. 2017;15:1807–1817.
   PubMed Web of Science ®Google Scholar
• Diaz JA, Wrobleski SK, Alvarado CM, et al. P-selectin inhibition therapeutically promotes thrombus resolution and prevents vein wall fibrosis better than enoxaparin and an inhibitor to von Willebrand factor. Arterioscler Thromb Vasc Biol. 2015;35:829–837.
   PubMed Web of Science ®Google Scholar
• Younis HS, Crosby J, Huh JI, et al. Antisense inhibition of coagulation factor XI prolongs APTT without increased bleeding risk in cynomolgus monkeys. Blood. 2012;119:2401–2408.
   PubMed Web of Science ®Google Scholar
• Büller HR, Bethune C, Bhanot S, et al. Factor XI antisense oligonucleotide for prevention of venous thrombosis. N Engl J Med. 2015;372:232–240.
   PubMed Web of Science ®Google Scholar
• Baglin TP, Langdown J, Frasson R, et al. Discovery and characterization of an antibody directed against exosite I of thrombin. J Thromb Haemost. 2016;14:137–142.
   PubMed Web of Science ®Google Scholar
• Verhamme P, Pakola S, Jensen TJ, et al. Tolerability and pharmacokinetics of TB-402 in healthy male volunteers. Clin Ther. 2010;32:1205–1220.
   PubMed Web of Science ®Google Scholar
• Jacquemin M, Benhida A, Peerlinck K, et al. A human antibody directed to the factor VIII C1 domain inhibits factor VIII cofactor activity and binding to von Willebrand factor. Blood. 2000;95:156–163.
   PubMed Web of Science ®Google Scholar
• Verhamme P, Tangelder M, Verhaeghe R, et al. Single intravenous administration of TB-402 for the prophylaxis of venous thromboembolism after total knee replacement: a dose-escalating, randomized, controlled trial. J Thromb Haemost. 2011;9:664–671.
   PubMed Web of Science ®Google Scholar
• Verhamme P, Gunn S, Sonesson E, et al. Single-dose TB-402 or rivaroxaban for the prevention of venous thromboembolism after total hip replacement. A randomised, controlled trial. Thromb Haemost. 2013;109:1091–1098.
   PubMed Web of Science ®Google Scholar
• Buchmueller A, Wilmen A, Strassburger J, et al. The anti-factor XIa antibody BAY 1213790 is a novel anticoagulant that shows strong antithrombotic efficacy without an increased risk of bleeding in rabbit models. Res Pract Thromb Haemost. 2017;1(Suppl.1): PB 096 [abstract]. 355–356.
   Google Scholar
• Thomas D, Thelen K, van der Mey D, et al. First evaluation of the safety, pharmacokinetics and pharmacodynamics of BAY 1213790, a full human IgG1 antibody targeting coagulation factor XIa, in healthy young men. Res Pract Thromb Haemost. 2017;1(Suppl.1): PB 834 [abstract]. 392.
   Google Scholar
• Tucker EI, Marzec UM, White TC, et al. Prevention of vascular graft occlusion and thrombus-associated thrombin generation by inhibition of factor XI. Blood. 2009;113:936–944.
   PubMed Web of Science ®Google Scholar
• Cheng Q, Tucker EI, Pine MS, et al. A role for factor XIIa-mediated factor XI activation in thrombus formation in vivo. Blood. 2010;116:3981–3989.
   PubMed Web of Science ®Google Scholar
• Leung PY, Hurst S, Berny-Lang MA, et al. Inhibition of factor XII-mediated activation of factor XI provides protection against experimental acute ischemic stroke in mice. Transl Stroke Res. 2012;3:381–389.
   PubMed Web of Science ®Google Scholar
• van Montfoort ML, Knaup VL, Marquart JA, et al. Two novel inhibitory anti-human factor XI antibodies prevent cessation of blood flow in a murine venous thrombosis model. Thromb Haemost. 2013;110:1065–1073.
   PubMed Web of Science ®Google Scholar
• Petitou M, Nancy-Portebois V, Dubreucq G, et al. From heparin to EP217609: the long way to a new pentasaccharide-based neutralisable anticoagulant with an unprecedented pharmacological profile. Thromb Haemost. 2009;102:804–810.
   PubMed Web of Science ®Google Scholar
• Gueret P, Combe S, Krezel C, et al. Neutralization of EP217609, a new dual-action FIIa/FXa anticoagulant, by its specific antidote avidin: a phase I study. Eur J Clin Pharmacol. 2017;73:15–28.
   PubMed Web of Science ®Google Scholar
• Wong PC, Quan ML, Watson CA, et al. In vitro, antithrombotic and bleeding time studies of BMS-654457, a small-molecule, reversible and direct inhibitor of factor XIa. J Thromb Thrombolysis. 2015;40:416–423.
   PubMed Web of Science ®Google Scholar
• Wong P, Quan M, Watson C. A small-molecule and direct inhibitor of factor XIa provides strong antithrombotic activity with low bleeding in non-human primate model of arterial thrombosis. Res Pract Thromb Haemost. 2017;1(Suppl.1). OC40.4 [abstract].
   Google Scholar
• Kouyama S, Ono T, Hagio T, et al. Discovery of ONO-5450598, a highly orally bioavailable small molecule factor XIa inhibitor: the pharmacokinetic and pharmacological profiles. Res Pract Thromb Haemost. 2017;1(Suppl.1): PB 2139 [abstract]. 99.
   Google Scholar
• Zhang T, Andre P, Bateman TJ, et al. Development of a novel class of potent and selective FIXa inhibitors. Bioorg Med Chem Lett. 2015;25:4945–4949.
   PubMed Web of Science ®Google Scholar
• Sakurada I, Endo T, Hikita K, et al. Discovery of novel aminobenzisoxazole derivatives as orally available factor IXa inhibitors. Bioorg Med Chem Lett. 2017;27:2622–2628.
   PubMed Web of Science ®Google Scholar
• Sousa HR, Gaspar RS, Sena EM, et al. Novel antiplatelet role for a protein disulfide isomerase-targeted peptide: evidence of covalent binding to the C-terminal CGHC redox motif. J Thromb Haemost. 2017;15:774–784.
   PubMed Web of Science ®Google Scholar
• Smith SA, Choi SH, Collins JN, et al. Inhibition of polyphosphate as a novel strategy for preventing thrombosis and inflammation. Blood. 2012;120:5103–5110.
   PubMed Web of Science ®Google Scholar
• Shenoi RA, Kalathottukaren MT, Travers RJ, et al. Affinity-based design of a synthetic universal reversal agent for heparin anticoagulants. Sci Transl Med. 2014;6(260):260ra150.
   PubMed Web of Science ®Google Scholar
• Travers RJ, Shenoi RA, Kalathottukaren MT, et al. Nontoxic polyphosphate inhibitors reduce thrombosis while sparing hemostasis. Blood. 2014;124:3183–3190.
   PubMed Web of Science ®Google Scholar
• Al-Horani RA, Gailani D, Desai UR. Allosteric inhibition of factor XIa. Sulfated non-saccharide glycosaminoglycan mimetics as promising anticoagulants. Thromb Res. 2015;136:379–387.
   PubMed Web of Science ®Google Scholar
• Al-Horani RA, Karuturi R, Lee M, et al. Allosteric inhibition of factor XIIIa. Non-saccharide glycosaminoglycan mimetics, but not glycosaminoglycans, exhibit promising inhibition profile. PLoS One. 2016;11:e0160189.
   PubMed Web of Science ®Google Scholar
• Sidhu PS, Abdel Aziz MH, Sarkar A, et al. Designing allosteric regulators of thrombin. Exosite 2 features multiple sub-sites that can be targeted by sulfated small molecules for inducing inhibition. J Med Chem. 2013;56:5059–5070.
   PubMed Web of Science ®Google Scholar
• Argade MD, Mehta AY, Sarkar A, et al. Allosteric inhibition of human factor XIa: discovery of monosulfated benzofurans as a class of promising inhibitors. J Med Chem. 2014;57:3559–3569.
   PubMed Web of Science ®Google Scholar
• Zhong C, Zhang L, Chen L, et al. Coagulation factor XI vaccination: an alternative strategy to prevent thrombosis. J Thromb Haemost. 2017;15:122–130.
   PubMed Web of Science ®Google Scholar
• Chen W, Carvalho LP, Chan MY, et al. Fasxiator, a novel factor XIa inhibitor from snake venom, and its site-specific mutagenesis to improve potency and selectivity. J Thromb Haemost. 2015;13:248–261.
   PubMed Web of Science ®Google Scholar
• Chen W, Goh LC, Kang TS, et al. Identification and characterisation of novel inhibitors on extrinsic tenase complex from Bungarus fasciatus (banded krait) venom. Thromb Haemost. 2014 Oct;112(4):700–715.
   PubMed Web of Science ®Google Scholar
• Woodruff RS, Sullenger BA. Modulation of the coagulation cascade using aptamers. Arterioscler Thromb Vasc Biol. 2015;35:2083–2091.
   PubMed Web of Science ®Google Scholar
• Bennett CF, Swayze EE. RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu Rev Pharmacol Toxicol. 2010;50:259–293.
   PubMed Web of Science ®Google Scholar
• Lippi G, Harenberg J, Mattiuzzi C, et al. Next generation antithrombotic therapy: focus on antisense therapy against coagulation factor XI. Semin Thromb Hemost. 2015;41:255–262.
   PubMed Web of Science ®Google Scholar
• Crosby J, Gao D, Zhao C, et al. Systematic evaluation of coagulation factors as targets for anti-thrombotic therapy using antisense technology. Blood (ASH Annual Meeting Abstracts). 2009;114: abstract 4181.
   Google Scholar
• Monia B, Zhang H, Zhao C, et al. ISIS 401025, a second generation antisense oligonucleotide targeting prothrombin, inhibits plasma prothrombin level and promotes anticoagulation in mice. Circulation. 2007;116(16Suppl): abstract716. II_134.
   Google Scholar
• Zhang H, Löwenberg EC, Crosby JR, et al. Inhibition of the intrinsic coagulation pathway factor XI by antisense oligonucleotides: a novel antithrombotic strategy with lowered bleeding risk. Blood. 2010;116:4684–4692.
   PubMed Web of Science ®Google Scholar
• Al-Horani RA, Desai UR. Factor XIa inhibitors: a review of the patent literature. Expert Opin Ther Pat. 2016;26:323–345.
   PubMed Web of Science ®Google Scholar
• Wang C, Corte JR, Rossi KA, et al. Macrocyclic factor XIa inhibitors. Bioorg Med Chem Lett. 2017;27:4056–4060.
   PubMed Web of Science ®Google Scholar
• Corte JR, Yang W, Fang T, et al. Macrocyclic inhibitors of factor XIa: discovery of alkyl-substituted macrocyclic amide linkers with improved potency. Bioorg Med Chem Lett. 2017;27:3833–3839.
   PubMed Web of Science ®Google Scholar
• Corte JR, Fang T, Osuna H, et al. Structure-based design of macrocyclic factor XIa inhibitors: discovery of the macrocyclic amide linker. J Med Chem. 2017;60(3):1060–1075.
   PubMed Web of Science ®Google Scholar
• Bekendam RH, Flaumenhaft R. Inhibition of protein disulfide isomerase in thrombosis. Basic Clin Pharmacol Toxicol. 2016;119(Suppl.3):42–48.
   PubMed Web of Science ®Google Scholar
• Wang L, Essex DW. A new antithrombotic strategy: inhibition of the C-terminal active site of protein disulfide isomerase. J Thromb Haemost. 2017;15:770–773.
   PubMed Web of Science ®Google Scholar
• Bachmann MF, Whitehead P. Active immunotherapy for chronic diseases. Vaccine. 2013;31:1777–1784.
   PubMed Web of Science ®Google Scholar
• Galabova G, Brunner S, Winsauer G, et al. Peptide-based anti-PCSK9 vaccines - an approach for long-term LDLc management. PLoS One. 2014;9:e114469.
   PubMed Web of Science ®Google Scholar
• Gottlieb M, Khishfe B. Idarucizumab for the reversal of dabigatran. Ann Emerg Med. 2017;69:554–558.
   PubMed Web of Science ®Google Scholar
• Douxfils J, Gosselin RC. Laboratory Assessment of direct oral anticoagulants. Semin Thromb Hemost. 2017;43:277–290.
   PubMed Web of Science ®Google Scholar
• Gómez-Outes A, Suárez-Gea ML, Lecumberri R, et al. Direct-acting oral anticoagulants: pharmacology, indications, management, and future perspectives. Eur J Haematol. 2015;95:389–404.
   PubMed Web of Science ®Google Scholar
• Yao X, Abraham NS, Alexander GC, et al. Effect of adherence to oral anticoagulants on risk of stroke and major bleeding among patients with atrial fibrillation. J Am Heart Assoc. 2016;5. DOI:10.1161/JAHA.115.003074.
   Web of Science ®Google Scholar
• Chowdhury R, Khan H, Heydon E, et al. Adherence to cardiovascular therapy: A meta-analysis of prevalence and clinical consequences. Eur Heart J. 2013;34:2940–2948.
   PubMed Web of Science ®Google Scholar
• Jackevicius CA, Tsadok MA, Essebag V, et al. Early non-persistence with dabigatran and rivaroxaban in patients with atrial fibrillation. Heart. 2017;103:1331–1338.
   PubMed Web of Science ®Google Scholar
• Cho SM, Moazami N, Frontera JA. Stroke and intracranial hemorrhage in HeartMate II and HeartWare left ventricular assist devices: a systematic review. Neurocrit Care. 2017;27:17–25.
   PubMed Web of Science ®Google Scholar
• Hess PL, Mirro MJ, Diener HC, et al. Addressing barriers to optimal oral anticoagulation use and persistence among patients with atrial fibrillation: proceedings, Washington, DC, December 3-4, 2012. Am Heart J. 2014;168:239–247.
   PubMed Web of Science ®Google Scholar