Drug evaluation: DU-176b, an oral, direct Factor Xa antagonist

Current Opinion in Investigational Drugs

Volumn 8, Issue 9, 2007, Pages 778-783

  Hylek, E ^a  

^a BOSTON UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 [4 [(1 ACETIMIDOYL 3 PYRROLIDINYL)OXY]PHENYL] 3 (7 AMIDINO 2 NAPHTHYL)PROPIONIC ACID; ACTIVATED PROTHROMBIN COMPLEX; ANTICOAGULANT AGENT; APIXABAN; BLOOD CLOTTING FACTOR 10A INHIBITOR; CHRISTMASSIN; DU 176B; FONDAPARINUX; LOW MOLECULAR WEIGHT HEPARIN; LY 517717; MELAGATRAN; PAMITEPLASE; PRT 054021; RECOMBINANT BLOOD CLOTTING FACTOR 8; RIVAROXABAN; TICLOPIDINE; UNCLASSIFIED DRUG; WARFARIN; YM 150; BLOOD CLOTTING FACTOR 10A;

ANTICOAGULATION; BLEEDING TIME; BRAIN HEMORRHAGE; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DOSE TIME EFFECT RELATION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG HALF LIFE; DRUG METABOLISM; DRUG SAFETY; DRUG SCREENING; DRUG SYNTHESIS; EXPERIMENTAL MOUSE; EXPERIMENTAL RAT; HUMAN; INTESTINE ABSORPTION; MONOTHERAPY; NONHUMAN; PHARMACODYNAMICS; REVIEW; SIDE EFFECT; STRUCTURE ACTIVITY RELATION; THROMBOEMBOLISM; THROMBOSIS PREVENTION; X RAY CRYSTALLOGRAPHY; ANIMAL; DRUG ANTAGONISM; METABOLISM; ORAL DRUG ADMINISTRATION; PATENT; TREATMENT OUTCOME; VEIN THROMBOSIS;

ADMINISTRATION, ORAL; ANIMALS; ANTICOAGULANTS; FACTOR XA; HUMANS; PATENTS; STRUCTURE-ACTIVITY RELATIONSHIP; THROMBOEMBOLISM; TREATMENT OUTCOME; VENOUS THROMBOSIS;

EID: 34548314559     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (36)

1. 158251 Dibasic (amidinoaryl) propanoic acid derivatives as novel blood coagulation Factor Xa inhibitors. Nagahara T, Yokoyama Y, Inamura K, Katakura S, Komoriya S, Yamaguchi H, Hara T, Iwamoto M J MED CHEM 1994 37 8 1200-1207
2. 323346 Recent advances in inhibitors of Factor Xa in the prothrombinase complex. Zhu BY, Scarborough RM CURR OPIN CARDIOVASC PULM RENAL INVEST DRUGS 1999 1 1 63-88
3. 484147 Factor Xa inhibitors: Today and beyond. Walenga JM, Jeske WP, Hoppensteadt D, Fareed J CURR OPIN INVEST DRUGS 2003 4 3 272-281
4. 567056 Orally active Factor Xa inhibitors: 4,5,6,7- tetrahydrothiazolo[5,4-c] pyridine derivatives. Haginoya N, Kobayashi S, Komoriya S, Hirokawa Y, Furugori T, Nagahara T BIOORG MED CHEM LETT 2004 14 11 2935-2939
5. 573101 Antithrombotic and hemorrhagic effects of DU-176b, a novel, potent and orally active direct Factor Xa inhibitor: A wider safety margin compared to heparins and warfarin. Furugohri T, Honda Y, Matsumoto C, Isobe K, Sugiyama N, Morishima Y, Shibano T BLOOD 2004 104 11 Abs 1851
6. 573105 Antithrombotic properties of DU-176b, a novel, potent and orally active direct Factor Xa inhibitor in rat models of arterial and venous thrombosis: Comparison with fondaparinux, an antithrombin dependent Factor Xa inhibitor. Fukuda T, Matsumoto C, Honda Y, Sugiyama N, Morishima Y, Shibano T BLOOD 2004 104 11 Abs 1852
7. 573107 In vitro characteristics, anticoagulant effects and in vivo antithrombotic efficacy of a novel, potent and orally active direct Factor Xa inhibitor, DU-176b. Morishima Y, Furugohri T, Isobe K, Honda Y, Matsumoto C, Shiozaki Y, Muramatsu S, Sugiyama N, Shibano T BLOOD 2004 104 11 Abs 1862
8. 638308 Worldwide sales of olmesartan to top ¥ 100 billion in 2006: Daiichi Sankyo. PHARMA JPN 2005 1968 1-3
9. 640490 Impact of antithrombin deficiency on efficacies of DU-176b, a novel orally active direct Factor Xa inhibitor, and antithrombin dependent anticoagulants, fondaparinux and heparin. Fukuda T, Honda Y, Matsumoto C, Sugiyama N, Matsushita T, Yanada M, Morishima Y, Shibano T BLOOD 2005 106 11 Abs 1874
10. 640496 A thrombin inhibitor, but not a Factor Xa inhibitor, DU-176b, aggravates tissue factor-induced hypercoagulation in rats. Morishima Y, Fukuda T, Tsuji N, Honda Y, Matsumoto C, Furugohri T, Shibano T BLOOD 2005 106 11 Abs 1878
11. 659999 Daiichi Sankyo Inc company website. Daiichi Sankyo Inc COMPANY WORLD WIDE WEB SITE 2006 April 03
12. 676138 Daiichi Sankyo group research & development pipeline. Daiichi Sankyo Co Ltd COMPANY WORLD WIDE WEB SITE 2006 March 31
13. 733058 Design, synthesis, and biological activity of novel Factor Xa inhibitors: Improving metabolic stability by S1 and S4 ligand modification. Komoriya S, Kobayashi S, Osanai K, Yoshino T, Nagata T, Haginoya N, Nakamoto Y, Mochizuki A, Nagahara T, Suzuki M, Shimada T et al BIOORG MED CHEM 2006 14 5 1309-1330
14. 733059 A phase-I study to assess the antithrombotic properties of DU-176b: An orally active direct Factor-Xa inhibitor. J AM COLL CARDIOL 2006 47 4 Suppl A Abs 908-161
15. 733061 Design, synthesis, and biological activity of non-basic compounds as Factor Xa inhibitors: SAR study of S1 and aryl binding sites. Komoriya S, Haginoya N, Kobayashi S, Nagata T, Mochizuki A, Suzuki M, Yoshino T, Horino H, Nagahara T, Suzuki M, Isobe Y et al BIOORG MED CHEM 2005 13 12 3927-3954
16. 733062 Synthesis and conformational analysis of a non-amidine Factor Xa inhibitor that incorporates 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine as S4 binding element. Haginoya N, Kobayashi S, Komoriya S, Yoshino T, Suzuki M, Shimada T, Watanabe K, Hirokawa Y, Furugori T, Nagahara T J MED CHEM 2004 47 21 5167-5182
17. 736678 A wide safety margin of a Factor Xa inhibitor, DU-176b, between antithrombotic effect and exacerbation of intracerebral hemorrhage in rats: Comparison with a thrombin inhibitor. Morishima Y, Shirasaki Y, Kito F, Honda Y, Shibano T CIRCULATION 2006 114 18 Suppl Abs 632/B101
18. 811466 Comparison of antithrombotic properties of a direct FXa inhibitor, DU-176b, with an antithrombin dependent FXa inhibitor, fondaparinux, in a capillary perfusion chamber thrombosis model. Shibano T, Tsuji N, Fukuda T, Morishima Y CONGRESS INT SOC THROMB HAEMOSTASIS 2007 21 Abs P-T-640
19. 811467 Effect of a Factor Xa inhibitor DU-176b on intracerebral hemorrhage in rats: A wider safety margin compared with a thrombin inhibitor. Morishima Y, Shirasaki Y, Kito F, Honda Y, Shibano T CONGRESS INT SOC THROMB HAEMOSTASIS 2007 21 Abs P-T-641
20. 811474 Effects of DU-176b, a novel direct Factor Xa inhibitor, on prothrombinase activity and platelet aggregation in vitro. Shibano T, Tsuji N, Kito F, Fukuda T, Furugohri T, Morishima Y CONGRESS INT SOC THROMB HAEMOSTASIS 2007 21 Abs P-T-642
21. 811628 Activated prothrombin complex concentrate, recombinant Factor VIII and Factor IX reverse prolonged clotting time induced by DU-176b, a direct Factor Xa inhibitor, in human plasma. Morishima Y, Fukuda T, Honda Y, Shibano Y CONGRESS INT SOC THROMB HAEMOSTASIS 2007 21 Abs P-T-639
22. 812200 Antithrombotic properties of DU-176b, a novel orally active Factor Xa inhibitor: Inhibition of both arterial and venous thrombosis, and combination effects with other antithrombotic agents. Morishima Y, Furugohri T, Honda Y, Matsumoto C, Isobe K, Fukuda T, Shiozaki Y, Muramatsu S, Sugiyama N, Shibano T J THROMB HAEMOST 2005 3 Suppl 1 Abs P0511
23. 812203 Recombinant Factor VIIa reverses Te prolonged bleeding time induced by high dose of DU-176b, a novel direct Factor Xa inhibitor, in rats. Morishima Y, Honda Y, Matsumoto C, Fukuda T, Isobe K, Kumada T, Shibano T J THROMB HAEMOST 2005 3 Suppl 1 Abs P0512
24. 812206 Antithrombotic effects of a direct Factor Xa inhibitor, DU-176b, and an antithrombin dependent Factor Xa inhibitor, fondaparinux, on an ex vivo capillary perfusion chamber thrombosis model in rats. Fukuda T, Matsumoto C, Honda Y, Morishima Y, Shibano T J THROMB HAEMOST 2005 3 Suppl 1 Abs P0612
25. 812208 Pharmacological characterization, antithrombotic and bleeding effects of DU-176b, a novel, potent and orally active direct inhibitor of Factor Xa: A wider safety margin of antithrombotic and bleeding effects compared to heparin, LMWH and warfarin. Furugohri T, Isobe K, Honda Y, Matsumoto C, Sugiyama N, Morishima Y, Shibano T J THROMB HAEMOST 2005 3 Suppl 1 Abs P1110
26. 814315 The pharmacology and management of the vitamin K antagonists: The seventh ACCP conference on antithrombotic and thrombolytic therapy. Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek EM CHEST 2004 126 204S-233S
27. 814319 What is all that thrombin for? Mann KG, Brummel K, Butenas S J THROMB HAEMOST 2003 1 7 1504-1514
28. 814323 Factor Xa is highly protected from antithrombin-fondaparinux and antithrombin-enoxaparin when incorporated into the prothrombinase complex. Brufatto N, Ward A, Nesheim ME J THROMB HAEMOST 2003 1 6 1258-1263
29. 815221 Inhibition of Factor Xa: A potential target for the development of new anticoagulants. Alexander JH, Singh KP AM J CARDIOVASC DRUGS 2005 5 5 279-290
30. 815225 NCT00107900: Study of the efficacy and safety of DU-176b in preventing blood clots in patients undergoing total hip replacement. Daiichi Sankyo Inc WWW.CLINICALTRIALS.GOV 2006 April 04
31. 815227 NCT00504556: Study to assess the safety of a potential new drug in comparison to the standard practice of dosing with warfarin for a diagnosis of non-valvular atrial fibrillation. Daiichi Sankyo Inc WWW. CLINICALTRIALS.GOV 2007 July 18
32. 815272 NCT00398216: A study of DU-176b in preventing blood clots after hip replacement surgery. Daiichi Sankyo Inc WWW.CLINICALTRIALS.GOV 2007 March 27
33. 816052 Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors. Weitz JI, Hudoba M, Massel D, Maraganore J, Hirsh J J CLIN INVEST 1990 86 2 385-391
34. 816287 Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S CIRCULATION 2007 115 21 2689-2696
35. 816290 New anticoagulants. Weitz JI, Bates SM J THROMB HAEMOST 2005 3 8 1843-1853
36. 816291 Oral, direct Factor Xa inhibitors in development for the prevention and treatment of thromboembolic diseases. Turpie AG ARTERIOSCLER THROMB VASC BIOL 2007 27 6 1238-1247