DX-9065a Daiichi

Current Opinion in Investigational Drugs

Volumn 4, Issue 9, 2003, Pages 1105-1112

  Kaiser, Brigitte ^a  

^a FRIEDRICH SCHILLER UNIVERSITY JENA   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

1 [3 (AMINOMETHYL)PHENYL] N [3 FLUORO 2' (METHYLSULFONYL)[1,1' BIPHENYL] 4 YL] 3 (TRIFLUOROMETHYL) 1H PYRAZOLE 5 CARBOXAMIDE; 2 [4 [(1 ACETIMIDOYL 3 PYRROLIDINYL)OXY]PHENYL] 3 (7 AMIDINO 2 NAPHTHYL)PROPIONIC ACID; ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; BLOOD CLOTTING FACTOR 10A INHIBITOR; ENOXAPARIN; FIBRINOGEN RECEPTOR ANTAGONIST; FONDAPARINUX; HEPARIN; PLACEBO; THROMBIN INHIBITOR;

ANGINA PECTORIS; ANTICOAGULATION; BINDING AFFINITY; BLEEDING; CLINICAL TRIAL; CORONARY ARTERY DISEASE; DISEASE MODEL; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG INDICATION; DRUG METABOLISM; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TOLERABILITY; EUROPE; HEART INFARCTION; HUMAN; IC 50; IN VITRO STUDY; IN VIVO STUDY; JAPAN; KIDNEY DYSFUNCTION; LIVER DYSFUNCTION; NONHUMAN; PHARMACODYNAMICS; REVIEW; SIDE EFFECT; STRUCTURE ACTIVITY RELATION; THROMBOCYTE COUNT; THROMBOEMBOLISM; THROMBOSIS; TOXICITY TESTING; TRANSLUMINAL CORONARY ANGIOPLASTY; UNITED STATES; UNSTABLE ANGINA PECTORIS;

ANGINA PECTORIS; ANTICOAGULANTS; CLINICAL TRIALS, PHASE I; CLINICAL TRIALS, PHASE II; FACTOR XA; HUMANS; MOLECULAR STRUCTURE; NAPHTHALENES; PROPIONIC ACIDS; RANDOMIZED CONTROLLED TRIALS; STRUCTURE-ACTIVITY RELATIONSHIP; THROMBOEMBOLISM;

EID: 0142183215     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (64)

1. 155837 Design and synthesis of an orally active Factor Xa inhibitor. Komoriya S, Yokoyama Y, Nagahara T, Yamaguchi H ACS 1994 207 MEDI 212
2. 158251 Dibasic (amidinoaryl) propinoic 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 This paper describes the synthesis and biochemical characterization of a series of dibasic (amidinoaryl) propanoic acid derivatives, including DX-9065a, with inhibitory activity against FXa.
3. 162461 Effects of DX-9065a, an orally active, newly synthesized and specific inhibitor of Factor Xa, against experimental disseminated intravascular coagulation in rats. Yamazaki M, Asakura H, Aoshima K, Saito M, Jokaji H, Uotani C, Kumabashiri I, Morishita E, Ikeda T, Matsuda T Thromb Haemost 1994 72 3 393-396
4. 165504 DX-9065a, a new synthetic, potent anticoagulant and selective inhibitor for Factor Xa. Hara T, Yokoyama A, Ishihara H, Yokoyama Y, Nagahara T, Iwamoto M Thromb Haemost 1994 71 3 314-319 The first comprehensive description of DX-9065a, which describes its inhibition kinetics for human serine proteases.
5. 187241 DX-9065a, an orally active, specific inhibitor of Factor Xa, inhibits thrombosis without affecting bleeding time in rats. Hara T, Yokoyama A, Tanabe K, Ishihara H, Iwamoto M Thromb Haemost 1995 74 2 635-639 A good description of the biological activity of DX-9065a in a thrombosis model in the rat.
6. 198743 Species differences in anticoagulant and anti-Xa activity of DX-9065a, a highly selective Factor Xa inhibitor. Hara T, Yokoyama A, Morishima Y, Kunitada S Thromb Res 1995 80 1 99-104
7. 198744 Molecular model of an interaction between Factor Xa and DX-9065a, a novel Factor Xa inhibitor. Katakura S, Nagahara T, Hara T, Kunitada S, Iwamoto M Eur J Med Chem 1995 30 387-394 An interesting docking study, which provides the molecular model of the inhibitor-FXa complex.
8. 200145 Importance of Factor Xa in determining the procoagulant activity of whole-blood clots. Eisenberg PR, Siegel JE, Abendschein DR, Miletich JP J Clin Invest 1993 91 5 1877-1883
9. 207559 Sanofi jumps into lead in race for Factor Xa inhibitor anticoagulants. Emerging Pharmaceuticals 1996 5 5 4-5
10. 227037 Annual Report 1996 - Daiichi Seiyaku Co. Daiichi Seiyaku Co Ltd Annual Report 1996 March
11. 272603 Antithrombotic and hemorrhagic effects of DX-9065a, a direct and selective Factor Xa inhibitor: Comparison with a direct thrombin inhibitor and antithrombin III-dependent anticoagulants. Morishima Y, Tanabe K, Terada Y, Hara T, Kunitada S Thromb Haemost 1997 78 5 1366-1371
12. 295049 New drugs in R&D pipeline. Pharma Jpn 1998 1609 Suppl 1-8
13. 298897 Role of thrombin compared with Factor Xa in the procoagulant activity of whole blood clots. Prager NA, Abendschein DR, McKenzie CR, Eisenberg PR Circulation 1995 92 4 962-967
14. 313313 DX 9065A, a novel, synthetic, selective and orally active inhibitor of Factor Xa: In vitro and in vivo studies. Herbert JM, Bernat A, Dol F, Herault JP, Crepon B, Lormeau JC J Pharmacol Exp Ther 1996 276 3 1030-1038 This paper presents comprehensive experimental studies of the efficacy of DX-9065a in vitro, concerning its inhibitory activity against FXa, and in vivo using various thrombosis and bleeding time models in different species.
15. 313318 The antithrombotic effect of synthetic low molecular weight human Factor Xa inhibitor, DX-9065a, on He-Ne laser-induced thrombosis in rat mesenteric vessels. Yamashita T, Tsuji T, Matsuoka A, Giddings JC, Yamamoto J Thromb Res 1997 85 1 45-51
16. 313319 Antithrombotic effects of orally active synthetic antagonists of activated Factor X in nonhuman primates. Yokoyama T, Kelly AB, Marzee UM, Hanson SR, Kunitada S, Harker LA Circulation 1995 92 3 485-491
17. 316111 X-ray structure of active site-inhibited clotting Factor Xa. Implications for drug design and substrate recognition. Brandstetter H, Kuhne A, Bode W, Huber R, Von Der Saal W, Wirthensohn K, Engh RA J Biol Chem 1996 271 47 29988-29992 The X-ray structure at 3.0 Å resolution of human FXa complexed with DX-9065a.
18. 320416 Drug development pipeline. Daiichi Pharmaceutical Co Ltd Company World Wide Web Site 1999 May 07
19. 321723 Activation of human vascular endothelial cells by Factor Xa: Effect of specific inhibitors. Herault JP, Bono F, Avril C, Schaeffer P, Herbert JM Biochem Pharmacol 1999 57 6 603-610 This paper describes the inhibitory effect of DX-9065a on the mitogenic action of FXa in cultured human vascular endothelial cells.
20. 323340 Factor Xa inhibitors: Today and beyond. Walenga JM, Jeske WP, Hoppensteadt D, Kaiser B Curr Opin Cardiovasc Pulm Renal Invest Drugs 1999 1 1 13-27
21. 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 Review of the discovery and development of amidino and non-amidino FXa inhibitors.
22. 329570 Synthetic inhibitors of thrombin and Factor Xa: From bench to bedside. Hauptmann J, Sturzebecher J Thromb Res 1999 93 5 203-241 An excellent review of preclinical and clinical aspects of thrombin and FXa inhibitors.
23. 330383 Factor Xa inhibitors. Al Obeidi F, Ostrem JA Exp Opin Ther Pat 1999 9 7 931-953
24. 50 value of 0.1 μM.
25. 349228 Japanese pharmaceutical industry. Lehman Brothers Inc 1999 August 25
26. 355833 Annual Report 1999 - Daiichi Pharmaceuticals. Daiichi Pharmaceutical Co Ltd Annual Report 1999 March 31
27. 359022 Protease inhibitors: Current status and future prospects. Leung D, Abbenante G, Fairlie DP J Med Chem 2000 43 3 305-341
28. 371924 27th National Medicinal Chemistry Symposium (Part II), Poster Session I - Highlights, Kansas City, MO, USA. Enuezie C IDDB Meeting Report 2000 June 13-17
29. 372415 Serine and cysteine protease inhibitors: The suitability of incorporating an electrophilic isostere in the design of therapeutic agents. Abbenante G, Leung D, March DR, Fairlie DP Nat Med Chem Symp 2000 27 A-09
30. 379183 Tolerability, pharmacokinetics, and pharmacodynamics of DX-9065a, a new synthetic potent anticoagulant and specific Factor Xa inhibitor, in healthy male volunteers. Murayama N, Tanaka M, Munitada S, Yamada H, Inoue T, Terada Y, Fujita M, Ikeda Y Clin Pharmacol Ther 1999 66 3 258-264 This paper reports the results of a phase I trial on the pharmacokinetics pharmacodynamics and tolerability of DX-9065a in healthy volunteers, which demonstrate that there is a good correlation between its linear pharmacokinetics and pharmacodynamics after intravenous administration.
31. 410595 DX-9065a, an orally active Factor Xa inhibitor, does not facilitate haemorrhage induced by tail transection or gastric ulcer at the effective doses in rat thrombosis model. Tanabe K, Morishima Y, Shibutani T, Terada Y, Hara T, Shinobara Y, Aoyagi K, Kunitada S, Kondo T Thromb Haemost 1999 81 5 828-834
32. 414406 Response in plasma-based coagulation measurements to DX-9065a, a novel factor Xa inhibitor, infused in patients with stable coronary artery disease. Becker RC, Bovill EG, Dyke CK, Gardner L, Walker ME, Robertson TL, Kunitada S, Ansell JE, Hochman JS, Kleiman NS, Armstrong PW, Harrington RA Thromb Haemost 2001 July 6-12 Abs P3096
33. 414413 Assessment of the pharmacodynamic profile of DX9065a, a direct Factor Xa inhibitor, in 36 healthy male subjects: A first study using subcutaneous route. Depasse F, Caplain H, Kunitada S, Samama MM Thromb Haemost 2001 July 6-12 Abs P3098
34. 415790 Effects of specific inhibitors on vascular effects of coagulation Factor Xa in vitro and in vivo. Schaeffer P, Bernat A, Dol F, Mares AM, Mauran G, Herbert JM Thromb Haemost 2001 July 6-12 Abs P1407
35. 457558 Comparison of pharmacokinetic (PK)/pharmacodynamic (PD) profiles for DX9065a, a novel direct Factor Xa inhibitor, between healthy male Japanese and Caucasian subjects. Depasse E, Brett M, Sato T, Kunitada S, Samama MM Int Union Angiology World Congress 2002 April 7-11 Abs 153
36. 459283 First experience with direct Factor Xa inhibition in patients with stable coronary disease: A pharmacokinetic and pharmacodynamic evaluation. Dyke CK, Becker RC, Kleiman NS, Hochman JS, Bovill EG, Lincoff AM, Gerstenblith G, Dzavik V, Gardner LH, Hasselblad V, Zillman LA et al Circulation 2002 105 20 2385-2391 This paper discusses the results of the first phase Ib trial in patients with stable coronary artery disease. After 60 h of a 72-h infusion, plasma DX-9065a levels correlated strongly with anti-FXa activity, PT and INR, but less so with APTT.
37. 460079 Development pipeline (Japan). Daiichi Pharmaceutical Co Ltd Company World Wide Web Site 2002 June 25
38. 460080 Development pipeline (Overseas). Daiichi Pharmaceutical Co Ltd Company World Wide Web Site 2002 June 25
39. 14C-DX-9065a in the healthy male volunteer after a single intravenous dose. Murayam N, McMahon H, Young CG, McCracken NW, Okamura Y, Hakusui H, Tanaka M Xenobiotica 2000 30 5 515-521
40. 462958 Effect of Factor Xa inhibitors on the platelet-derived microparticles procoagulant activity in vitro and in vivo in rats. Herault JP, Perrin B, Jongbloet C, Pflieger AM, Bernat A, Herbert JM Thromb Haemost 2000 84 668-674
41. 470484 American Heart Association Scientific Sessions 2002 (Part I) - Overnight Report, Chicago, IL, USA. Paterson D IDDB Meeting Report 2002 November 17-20
42. 481185 The design of competitive, small-molecule inhibitors of coagulation Factor Xa. Pauls HW, Ewing WR Curr Top Med Chem 2001 1 2 83-100
43. 481187 Recent advances in clinical trials of the direct and indirect selective Factor Xa inhibitors. Porcari AR, Chi L, Leadley R Expert Opin Investig Drugs 2000 9 7 1595-1600
44. 481188 Prolonged activation of prothrombin on the vascular wall after arterial injury. Ghigliotti G, Waissbluth AR, Speidel C, Abendschein DR, Eisenberg PR Arterioscler Thromb Vasc Biol 1998 18 2 250-257
45. 481189 Inactivation of Factor Xa by the synthetic inhibitor DX-9065a causes strong anticoagulant and antiplatelet actions in human blood. Kaiser B, Jeske W, Walenga JM, Fareed J Blood Coagul Fibrinolysis 1999 10 8 495-501
46. 481190 Inhibition of thrombin generation in plasma by inhibitors of Factor Xa. Prasa D, Svendsen L, Sturzebecher J Thromb Haemost 1997 78 4 1215-1220
47. 481193 Effects of a Factor Xa inhibitor, DX-9065a, in a novel rabbit model of venous thrombosis. Rogers KL, Chi L, Rapundalo ST, Kramer JB, Gallagher KP Basic Res Cardiol 1999 94 1 15-22
48. 481195 Antithrombotic effects of DX-9065a, a direct Factor Xa inhibitor: A comparative study in humans versus low molecular weight heparin. Shimbo D, Osende J, Chen J, Robbins J, Shimoto Y, Kunitada S, Fuster V, Badimon JJ Thromb Haemost 2002 88 5 733-738
49. 481198 Studies on the different modes of action of the anticoagulant protease inhibitors DX-9065a and argatroban. I. Effects on thrombin generation. Nagashima H J Biol Chem 2002 277 52 50439-50444
50. 481199 Studies on the different modes of action of the anticoagulant protease inhibitors DX-9065a and argatroban. II. Effects on fibrinolysis. Nagashima H J Biol Chem 2002 277 52 50445-50449
51. 481201 Effector protease receptor 1 mediates the mitogenic activity of Factor Xa for vascular smooth muscle cells in vitro and in vivo. Herbert JM, Bono F, Herault JP, Avril C, Dol F, Mares AM, Schaeffer P J Clin Invest 1998 101 5 993-1000
52. 481202 A synthetic inhibitor of Factor Xa, DX-9065a, reduces proliferation of vascular smooth muscle cells in vivo in rats. Kaiser B, Paintz M, Scholz O, Kunitada S, Fareed J Thromb Res 2000 98 2 175-185
53. 481205 Protective effects of DX-9065a, an orally active, novel synthesized and selective inhibitor of Factor Xa, against thromboplastin-induced experimental disseminated intravascular coagulation in rats. Yamazaki M, Asakura H, Aoshima K, Saito M, Jokaji H, Uotani C, Kumabashi I, Morishita E, Ikeda T, Matsuda T Semin Thromb Hemost 1996 22 3 255-259
54. 481207 Antithrombotic actions of selective inhibitors of blood coagulation factor Xa in rat models of thrombosis. Wong PC, Crain EJ, Nguan O, Watson CA, Racanelli A Thromb Res 1997 83 2 117-126
55. 481210 Antithrombotic drug market. Collins B, Hollidge C Nat Rev Drug Disc 2003 2 1 11-12
56. 481785 World-class people can find world-class drugs: Mr Morita of Daiichi. Pharma Jpn 2003 1832 1
57. 484147 Factor Xa inhibitors: Today and beyond. Walenga JM, Jeske WP, Hoppensteadt D, Fareed J Curr Opin Invest Drugs 2003 4 3 272-281
58. 498051 Effect of the direct Factor Xa inhibitor, DX-9065a, on thrombin generation in patients with stable coronary artery disease. Alexander JH, Becker RC, Hasselblad V, Dyke CK, Robertson TL, Harrington RA, Bovill EG J Thromb Hemost 2003 1 Suppl 1 Abs P2017
59. 498093 DX-9065a, a direct factor Xa inhibitor prevents both arterial and venous thrombosis in rats via blocking prothrombinase complex activity comparison with fondaparinux, an antithrombin dependent factor Xa inhibitor. Fukuda T, Honda Y, Matsumoto C, Ishihara H, Sugiyama N J Thromb Hemost 2003 1 Suppl 1 Abs P2045
60. 499385 Initial experience with a novel direct Factor Xa inhibitor in percutaneous coronary intervention. Alexander JH, Dyke CK, Becker RC, Yang H, Robertson TL, Kunitada S, Zillman LA, Cohen EA, Bovill EG, Berger PB, Lincoff M et al. J Am Coll Cardiol 2002 39 Suppl 1 Abs 887-6
61. 499395 Novel anti-coagulant clears hurdle. Duke University Medical Center Press Release 2002 March 20
62. 499402 New anti-clotting agent shows promise. Duke University Medical Center Press Release 2001 September 05
63. 499560 Global anticoagulant effects of a synthetic anti-Factor Xa inhibitor (DX-9065a): Implications for interventional use. Tobu M, Iqbal O, Ma Q, Schultz C, Jeske W, Hoppensteadt D, Lewis B, Fareed D, Fareed J Clin Appl Thromb Hemost 2003 9 1 1-17
64. 499561 Enhanced endogenous thrombolysis induced by a specific Factor Xa inhibitor, DX-9065a, evaluated in a rat arterial thrombolysis model in vivo. Hashimoto M, Onobayashi Y, Qiwa K, Giddings JC, Yamamoto J Thromb Res 2002 106 2 165-168