Fibrinogen receptor antagonists

References

• MORAN J: Thrombolytic treatment: the market, clinicalbackground and future therapies. In: Scrip (1990) PJB Publications, New York.
   Google Scholar
• PLOW EF, PIERSCHEiACHER MD, RUOSHLATI E, MAR-GUERIE G, GINSBERG MH: Arginyl-glycyl-aspartic acid sequences and fibrinogen binding to platelets. Blood (1987) 70:110–115.
   PubMed Web of Science ®Google Scholar
• ANDRIELTX A, CHARON MH, HUDRY-CLERGEON G, CHAPEL A, MARGUER1E G: Structural requirements of fibrinogen sequences implicated in platelet receptor recognition. Colloque INSERM (1989) 174:567–570.
   Google Scholar
• FEIGEN LP, NICHOLSON NS, TAITE BB, PANZER-ICNODLE SG, KING LW, SALYERS AK, GORCZYNSKI RJ, ADAMS SP: Inhibition of the platelet glycoprotein (IIb/IIIa GPTIb/Illa) receptor by an analog to RGDS. FASEB J. (1989) :3, A309.
   Google Scholar
• TRIPLETT DA: The platelet: a review. In: Platelet Function Laboratory Evaluation and Clinical Application (1978) Tri-plett DA (Ed), American Society of Clinical Pathologists: Chicago:1–33.
   Google Scholar
• Biochemistry of Platelets (1986) Phillips DR, Shuman MA (Eds), Academic Press: Orlando.
   Google Scholar
• Hemastasis and Thrombosis: Basic Principles and Clinical Practice (1982) Colman RW, Hirsh J, Marder VJ, Salzman EW (Eds), JB Lippincott Co.: Philadelphia.
   Google Scholar
• This book is an excellent general reference for background reading in the area of thrombosis.
   Google Scholar
• LIDON RM, ADELMAN B, MARAGANOFtE J, THEROUX P: Hirulog, a direct thrombin inhibitor, for the manage-ment of unstable angina. Circulation (1992) 86:14538.
   Google Scholar
• JAKUBOWSKI JA, SMITH GF, SAIL DJ: Future antithrom- botic therapy. In: Ann. Rep. Med. Chem. (1992) 27:99-108. An excellent broad review which covers Factor Xa inhibitors, thrombin inhibitors, and fibrinogen receptor antagonists prior to 1992.
   Google Scholar
• TAPPARELLI C, METTERNICH R, EHRHARDT C, COOK NS:
   Google Scholar
• Synthetic low-molecular weight thrombin inhibitors: molecular design and pharmacological profile. TIPS (1993) 14:366.
   PubMed Web of Science ®Google Scholar
• ISIHARA H, HARA T, YOKOYAMA A, NAGAHARA T, IWAMOTO M: Prolongation of coagulation time due tothe inhibition of factor Xa by DX-9065a, an orally active synthetic anticoagulant specific for factor Xa. 7bromb. Haernostasis (1993) 69(6):a469.
   Google Scholar
• This account marks the first disclosure of a selective orally active factor Xa inhibitor.
   Google Scholar
• ISIS-2 COLLABORATIVE GROUP: Randomized trial of In-travenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet (1988) (2):349–360.
   Google Scholar
• Aspirin (160 mg/day for a month) reduced the number of vascular deaths from 11.8% for placebo tablets to 9.4% over a thirty-five day period immediately following an MI. Further comparisions of pla-cebo infusion and placebo tablets - 13.2% vascular deaths and streptokinase (1.5 MU) and aspirin - 8.0% vascular deaths, demon-strate an additive benefit when compared with a 9.2% vascular death observed with streptokinase alone. Although aspirin is showing beneficial results, there is considerable room for improvement in the outcome of treatment following an MI.
   Google Scholar
• RUGGERI ZM: Mechanisms of shear-induced platelet adhesion and aggregation. Thrombosis and Haemostasis(1993) 70(1):119–123.
   PubMed Web of Science ®Google Scholar
• A detailed review which proposes a mechanism of shear induced platelet aggregation: 1) multimeric vWf binds to GP lb under high shear stress which induces the opening of a Ca2+ channel; 2) the increase in intracellular calcium leads to a functional change in GP llb-111a receptor such that it can bind vWf; 3) vWf binding to GP ilb-111a mediates platelet aggregation.
   Google Scholar
• WEISS HJ, HOFFMANN T, YOSHIOKA A, RUGGERI ZM: Evidence that the arg1744giy1745as _p1746 sequence in the GP Hb-ma binding domain of von Willebrand factor is Involved in platelet adhesion and thrombus formation on subendothelium. J. Lab. Clin. Med. 122(3):324–332.
   Google Scholar
• IKEDA Y, HANDA M, KAWANO K, MURATA M, ARAKI Y, ANBO H, KAWAI Y, WATANABE K, ITAGAKI I, SAKAI K, RUGGERI ZM: The role of von WiRebrand factor and fibrinogen in platelet aggregation under varying shear stress. J. Clin. Invest. (1991) 87:1234–1240.
   PubMed Web of Science ®Google Scholar
• STRONY J, ADELMAN B, PHILLIPS DR, SCARBOROUGH RM, CHARO IF: Inhibition of platelet thrombus formation in an in vivo model of high shear stress by a glycoprotein Iib-ma specific peptide antagonist. Circulation (1992) 861-1035a.
   Google Scholar
• An excellent study demonstrating a proportionality between shear stress and fibrinogen receptor antagonist dose required to block thrombus formation.
   Google Scholar
• SIMS PJ, GINSBERG MH, PLOW EF, SHATTIL SJ: Effect ofplatelet activation on the conformation of the plasma membrane glycoprotein Hb-Ma complex. J. Biol. Chem. (1991) 266:7345.
   PubMed Web of Science ®Google Scholar
• SHATTTL SJ, HOXIE JA, CUNNIGHAM M, BRASS LF: Changes in the platelet membrane glycoprotein Hb-Ma complex during platelet activation. J. Biol. Chem. (1985) 260:1107.
   Web of Science ®Google Scholar
• KOUNS WC, JENNINGS IX: Activation-independent ex-posure of the GP 11b-ma fibrinogen receptor. Tbromb. Res. (1991) 63:343.
   PubMed Web of Science ®Google Scholar
• HAWIGER J, KLOCZEWIAK M, BEDNAREK MA, TimmoNs s: Platelet receptor recognition domains on the a chain of human fibrinogen: structure-function analysis. Bio-chemistry (1989) 28:2909–2914.
   Google Scholar
• ANDRIEUX A, HUDRY-CLERGEON G, RYC10EWAERT J-J, CHAPEL A, GINSBERG MH, PLOW EF, MARGUERIE G: Amino acid sequences in fibrinogen mediating its in- teraction with its platelet receptor, GPJ. Biol.Chem. (1989) 264:9258.
   Google Scholar
• SAERRF; TRIELSRMISACIIÈR MD: New perspectives in cell adhesion: RGD and integrins. Science (1987) 238:491–497.
   Google Scholar
• WILLIAMS DH: The molecular basis of biological order. Aldrichimica Acta (1991) 24:71–80.
   Google Scholar
• An excellent review with thought provoking discussion regarding conformationally constrained ligands, solvation energy and ligand-receptor interactions.
   Google Scholar
• WILLIAMS DH, SEARLE MS: The cost of conformational order: entropy changes in molecular associations. J. Am. Chem. Soc. (1992) 114:10690–10697.
   Web of Science ®Google Scholar
• FARMER PS: Bridging the gap between bioactive peptides and nonpeptides: some perspectives in design. In: Drug Design (1980) Ariens EJ (Ed.), Academic Press, New York:119–142.
   Google Scholar
• A useful reference for background reading in peptide mimetics.
   Google Scholar
• PHILLIPS DR, CHARO IF, PARISE LV, FITZGERALD LA: Theplatelet membrane glycoprotein Ilb-ma complex. Blood (1988) 71:831–843.
   PubMed Web of Science ®Google Scholar
• O'TOOLE TE, LOFTUS JC, PLOW EF, GLASS AA, HARPER JR,GINSBERG MH: Efficient surface expression of platelet GPIIb-Ma requires both subunits. Blood (1989) 74(1):14–18.
   PubMed Web of Science ®Google Scholar
• D'SOUZA SED, GINSBERG MH, MATSEUDA GR, PLOW EF: A discrete sequence in a platelet integrin is involved in ligand recognition. Nature (1991) 350:66–68.
   PubMedGoogle Scholar
• D'SOUZA SED, GINSBERG MH, BURKE TA, PLOW EF: The ligand binding site of the platelet integrin receptor GP Hb-ma is proximal to the second calcium binding domain of its a subunit. J. Biol. Chem. (1990) 265(0:3440–3446.
   PubMedGoogle Scholar
• D'SOUZA SED, GINSBERG MM, LAM SCT, PLOW EF: Chemi-cal cross-linking of arginyl-glycyl-aspartic add pep-tides to an adhesion receptor on platelets Biol. Chem. (1988) 263(8):3943–3951.
   Google Scholar
• D'SOUZA SED, GINSBERG MH, BURKE TA, LAM SCT, PLOWEF: Localization of an arg-gly-asp recognition site within an integrin adhesion receptor. Science (1988) 242:91–93.
   PubMed Web of Science ®Google Scholar
• GINSBERG MH, DUX, PLOW EF: Cutr. Opin. Cell Biol. (1992)4:766–771.
   PubMedGoogle Scholar
• DUSTIN ML, SPRINGER TA: T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Na-tun, (1989) 341:619–624.
   PubMed Web of Science ®Google Scholar
• FOX JEB, UPFERT L, CLARK EA, REYNOLDS CC, AUSTIN CD, BRUGGE JS: On the role of the platelet membrane skeleton in mediating signal transduction. J.Bio/. Chem. (1993) 268(34):25973–25984.
   PubMed Web of Science ®Google Scholar
• DU X, GU M, WEISEL JW, NAGASWAMI C, BENNETT JS, BOWDITCH R, GINSBERG MH: Long range propagation of conformation changes in integrin am403. J.Biol. Chem. (1993) 268(31):23087–23092.
   PubMed Web of Science ®Google Scholar
• DU X, PLOW EF, FRELINGER III AL, O'TOOLE TE, LOFTUS JC, GINSBERG MH: Ligands 'activate' integrin ah133 (plate-let GPIlb-ma). Cell (1991) 65:409–416.
   PubMed Web of Science ®Google Scholar
• Demonstration that simple RGD containing peptides can function as partial agonists by inducing a conformational change in GP Ilb-IIIa to a form that has a high affinity for fibrinogen.
   Google Scholar
• GINSBERG MH, O'TOOLE TE, LOFTUS JC, PLOW EF: Ligand binding to integrins: dynamic regulation and common mechanisms. Cold Spring Harb. Sy. (1992) LVII:221–231.
   Google Scholar
• FRELINGER AL, LAM SC-T, PLOW EF, SMITH MA, LOFTUS JC, GINSBERG MH: Occupancy of an adhesive protein receptor modulates expression of an antigenic site involved in cell adhesion. J. Biol. Chem. (1988) 263:12397–12402.
   PubMed Web of Science ®Google Scholar
• FRELINGER AL, COHEN I, PLOW EF, SMITH MA, ROBERTS J, LAM SC-T, GINSBERG MH: Selective inhibition of hate-grin function by antibodies specific for ligand-occupied receptor conformers. J. Biol. Chem. (1990) 265:6346–6352,
   PubMed Web of Science ®Google Scholar
• KOUNS WC, WALL CD, WHITE MM., FOX CF, JENNINGS LK: A conformation dependent epitope of GP Ilb-Ma. J. Biol. Chem. (1990) 265:20594–20601.
   Google Scholar
• KOUNS WC, FOX CF, LAMOREAUX 'WJ, COONS LB, JEN-NINGS LK: The effect of GP Hb-ma receptor occupancy on the cytoskeleton of resting and activated platelets. J. Biol. Chem. (1991) 266:13891–13899.
   PubMed Web of Science ®Google Scholar
• SHADLE PJ, GINSBERG MH, PLOW EF, BARONDES SH: Platelet collagen adhesion: inhibition by a monoclonal antibody that binds glycoprotein fib. J. Cell Biol. (1984) 99:2056–2060.
   PubMed Web of Science ®Google Scholar
• FRELINGER AL, DU X, PLOW EF, GINSBERG MH: Mono-clonal antibodies to ligand-occupied conformers of integrin alibi33 J. Biol. Chem. (1991) 266:17106–17111.
   Google Scholar
• FRIEDMAN P: In vitro and in vivo studies with novelfibrinogen receptor antagonists and factor Xa inhibi-tors. Circulation (1990) 841-1035a.
   Google Scholar
• SABA TM: Plasma fibronectin and hepatic kupfer cell function. Prog. Liv. Dis. (1982) 7:109–131.
   PubMedGoogle Scholar
• SCHMIDT EE, MACDONALD IC, GROOM AC: Changes in spicule microcirculatory pathways in chronic idi-opathic thrombocytopenia purpura. Blood (1991) 78(6):1485–1489.
   PubMed Web of Science ®Google Scholar
• KOUNS WC, ROUX S, STEINER B: Human platelet GP Ilb-IlIa receptor blockade as a therapeutic strategy. Curr. Opin. Invest. Drugs (1993) 2(5):475–494.
   Google Scholar
• An excellent review focusing on studies with 7E3, Integrelin and Ro 44-9883/Ro 43–5054.
   Google Scholar
• COLLER BS, PEERSCHICE El, SCUDDER LE, SULLIVAN CA: A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets and induces a thrombasthenic-like state in normal platelets and binds to glycoproteins lib and/or Ma. J. Clin. Invest. (1983) 72:325–338.
   PubMed Web of Science ®Google Scholar
• COLLER BS: Anew murine monoclonal antibody reports an activation-dependent change in the conformation and/or microenvironment of the glycoprotein Itb/Ma complex. j din. Invest (1985) 76:101–108.
   PubMed Web of Science ®Google Scholar
• TCHENG JE, TOPOL EJ, KLEIMAN NS, ELLIS SG, NAVETTA Fl, FINTEL DJ, WEISMAN, HP, ANDERSON, K, WANG AL, MILLER JA, SIGMON ICN, CALIFF RM and EPIC INVESTIGA-TORS: Improvement in outcomes of coronary angioplasty by treatment with the GPITh/Ma inhibitor chimeric 7E3: multivariabk analysis of the EPIC study. Circulation (1993) 88(4):1I-a2727.
   Google Scholar
• Centorx benefits in unstable angina. Scrip (1992) 1753:29.
   Google Scholar
• TCHENG JE, ELLIS SG, KLEIMAN NS, HARRINGTON RA,MICK MJ, NAVETTA FL WORLEY S, SMITH JE, ICEREIAKES DJ, KITT MM, MILLER JA, SIGMON ICN, CALIFF RM, TOPOL EJ: Outcome of patients with the GP 11b/ma inhibitor Integrelin during coronary angioplasty: results of the IMPACT study. Circulation (1993) 88(4):II-a3200.
   Google Scholar
• BERNARDI MM, CALIFF RM, KLEIMAN N, ELLIS SG, TOPOL El: Lack of usefulness of prolonged bleeding times in predicting hemorrhagic events in patients receiving the 7E3 glycoprotein Hb/Hla platelet antibody. Am. J. Cardiol. (1993) 72(15):1121–1125.
   PubMed Web of Science ®Google Scholar
• This study makes a strong statement against correlating an increased bleeding time with an increase in bleeding events.
   Google Scholar
• SCHULMAN SP, GOLDSCHMIDT-CLERMONT PJ, NAVETIA FL CHANDRA NC, GUERCI AD, CALIFF RM, FERGUSON 3, WILLERSON JT, WOLFE CL, BAHR R, YAKUBOV SJ, NY-GAARD TVG', MASON SJ, BRASHEARS L, CHARO I, DU MEE C, KITT MM: Integrelin in unstable angina: a double-blind randomized trial. Circulation (1993) 88(4):II-a3272.
   Google Scholar
• DELANTY N, JENNINGS L, MORAN N, CATELLA F, FITZGER- ALD DJ: Antagonism of the platelet glycoprotein receptor in unstable angina: effects on platelet activity and receptor conformation. Circulation (1993) 88(4):II-a1705.
   Google Scholar
• Although a small study, the concept of inducing a conformational in the receptor upon ligand binding without an increase in platelet activation has been demonstrated.
   Google Scholar
• HARTMAN GD, EGBERTSON MS, HALC7ENKO W, LASWELL WL, DUGGAN ME, SMITH RI, NAYLOR AM, MANNO PD, LYNCH RJ, ZHANG G, CHANG CT-C, GOULD RJ: Non-peptide fibrinogen receptor antagonists. L Discovery and design of exosite inhibitors./ Med. Chem. (1992) 35:4640–4642.
   Google Scholar
• A good paper which illustrates the importance of directed screening providing novel, unobvious peptide mimetic starting points.
   Google Scholar
• PEERLINCK K, DE LEPEIEIRE I, GOLDBERG M, PANEBI-ANCO D, VERM'YLEN J, ARNOUT J: Activity and safety of L-700,462, a selective GPIIb-IlIa antagonist. Circulation (1992) 86:1–260.
   PubMedGoogle Scholar
• PEERLINCK K, ARNOUT J, DE LEPEIEIRE I, GOLDBERG M,FITZPATRICK V, VERMYLEN J: Combined effect of aspirin and MK 383 (L-700,462), a selective GP fib/ma antago-nist, in healthy volunteers. Thromb. Haemostas. (1993) 69(6):a67.
   Google Scholar
• AUG L, EDENHOFER A, HADVARY P, HURZELER M, KNOPP D, MULLER M, STEINER B, TRZECIAK A, WELLER T: Low molecular weight, non-peptide fibrinogen antagonists. J. Med. Chem. (1992) 35:4393–4407.
   PubMed Web of Science ®Google Scholar
• KOUNS WC, WET 1 FR T, HADVARY P, JENNINGS LK, STE- INER B: Identification of a peptidomimetic inhibitor with minimal effects on the conformation of Blood (1992) 80:165a.
   Google Scholar
• In this study, reversible conformational changes in the GP 11b-111a receptor were documented by monitoring the induction of a LIBS recognized by the D3 monoclonal antibody upon binding to Ro 43–5054; however, these effects were not observed with Ro 44–9883.
   Google Scholar
• JONES CR, AMBROS, RJ, RAPOLD HJ, STEINER B, WELLER T, VAN HEIN1NGEN P, CRIJINS HJMJ, JONKMAN JHG, HADVARY P: Ro 44-9883: a novel non peptide GPIlb/Dia antagonist in man. Thromb. Haemostas. (1993) 69(6):a65.
   Google Scholar
• CARTEAUX J-P, ROUX S, KUHN H, TSCHOPP T, COLOMBO V, HADVARY P: Ro 44-9883, anew nonpeptide glycopro-tein 1113/111a antagonist, prevents platelet loss during experimental cardiopulmonary bypass. J. of Thoracic and Cardiovascular Sutg . (1993) 106(5):834–841.
   PubMed Web of Science ®Google Scholar
• This study demonstrates potential new indications for fibrinogen receptor antagonists.
   Google Scholar
• NIEWIAROWSKI 5: Invited letter concerning: fibrinogen receptor antagonists in cardiopulmonary bypass. J. Tborac. Cardiovasc. Surg. (1993) 106:931–48.
   PubMed Web of Science ®Google Scholar
• ZABLOCKI JA, MIYANO M, GARLAND RB, PIREH D, SCHRETZMAN L, RAO SN, L1NDMARK RJ, PANZER-KNODLE SG, NICHOLSON NS, TAITE BB, SALYERS AK, KING LW, CAMPION JG, FEIGEN LP: Potent in vitro and in vivo Inhibitors of platelet aggregation based upon the arg-gly-asp-phe sequence of fibrinogen. A proposal on the nature of the binding interaction between the arg-guanidine of RGDX mimetics and the platelet GP lib-ffla receptor. J. Med. Chem. (1993) 36:1811–1819.
   Google Scholar
• ZABLOCKI JA, MIYANO M, GARLAND RB, PIREH D, SCHRETZMAN L, BOVY P, RICO JG, LINDMARK RJ, TJOENG FS, MCMACKINS DE, TOTH MV, NICHOLSON NS, PANZER-KNODLE S, TAITE B, SALYERS A, KING L, FEIGEN LP: Fibrinogen receptor antagonists - SAR of a new orally active series. 205th ACS Meeting, Denver, Medi - 3, Mar. 29th, 1993.
   Google Scholar
• CHENG S, CRAIG WS, MULLEN D, TSCHOPP JF, DIXON D, PIERSCHBACHER MD: Design and synthesis of novel cyclic RGD-containing peptides as highly potent and selective integrin a nb133 antagonists. J. Med. Chem. (1994) 37:1–8.
   PubMed Web of Science ®Google Scholar
• In this study, the authors have demonstrated a separation of fibrino-gen receptor antagonist concentration that inhibits platelet aggrega-tion from one that induces a marked enhancement of bleeding time.
   Google Scholar
• TSCHOPP JF, DRISCOLL EM, MU D-X, BLACK SC, PIERSCHBACHER MD, LUCCHESI BR: Inhibition of coro-nary artery reocclusion after thrombolysis with an RGD-containing peptide with no significant effect on bleeding time. Corrmary Artery Disease (1993) 4:809–817.
   PubMed Web of Science ®Google Scholar
• WHITE HD, CHARBONNIER B, VAN DE WERE F, ERHARDT L, DAVID D, HILLIS WS, VON DER LIPPE G, VERHEUGT F97A, JENNINGS G, BRAUN D, FITZPATRICK V, SAX FL: An aspirin-controlled study of MK-852 in patients with unstable angina. Circulation (1993) 813(4):11–a1074.
   Google Scholar
• Scrip-on-line Plus.
   Google Scholar
• CALLAHAN JF, NEWLANDER KA, BURGESS JL, EGGLESTON DS, NICHOLS A, WONG A, HUFFMAN WE: The use of y-turn mimetics to define peptide secondary structure. Tetra-hedron (1993) 49:3479–3488.
   Web of Science ®Google Scholar
• KU TW, ALI FE, BARTON LS, BEAN JW, BONDINELL WE, BURGESS JL, CALLAHAN JF, CALVO RR, CHEN L, EG-GLESTON DS, GLEASON JG, HUFFMAN WE, HWANG SM, JAKAS DR, KARASH, CB, 10EENAN, RM, KOPPLE KD, MITI FR WH, NEWLANDER ICA, NICHOLS A, PARKER ME, PEISHOFF CE, SAMANEN JM, UZINSICAS I, VENSLAVS1CY JW: Direct design of a potent non-peptide fibrinogen receptor antagonist based on the structure and conformation of a highly constrained cyclic RGD peptide. J. Am. Chem Soc. (1993) 115:8861–8862.
   Web of Science ®Google Scholar
• CALLAHAN JF, BEAN JW, BURGESS JL, EGGLESTON DS, MEI HWANG S, KOPPLE KD, KOSTER PF, NICHOLS A, PEISHOFF CE, SAMANEN JM, VASKO JA, WONG A, HUFFMAN WE: Design and synthesis of a C7 mimetic for the predicted T-turn conformation found in several constrained RGD antagonists. J. Med. Chem. (1992) 35:3970–3972.
   PubMed Web of Science ®Google Scholar
• BLACKBURN BK, MCDOWELL RS: The design and synthe-sis of non-peptidic GPantagonists. 205th ACSMeeting, Denver, Medi -4, Mar. 29th, 1993.
   Google Scholar
• MCDOWELL RS, GADEK TR: Structural studies of potent constrained RGD peptides. J. Am. Chem. Soc. (1992) 114:9245–9253.
   Web of Science ®Google Scholar
• BARKER PL, BUT TENS 5, BUNTING S, BURDICK DJ, CHAN KS, DEISHER T, EIGENBROT GADEK TR, GANTZOS R, LIPARI MT, MUIR CD, NAPIER MA, PITTI RM, PADUA A, QUAN C, STANLEY M, STRUBLE M, TOM JYK, BURNIER JP: CyclicRGD peptide analogues as antiplatelet antithrom-botics. J. Med. Chem. (1992) 35:2040.
   PubMed Web of Science ®Google Scholar
• BLACKBURN BK, BARKER P, GADEK T, MCDOWEIT RS, MCGEE L, SOMERS T, WEBB R, ROBARGE K: (1993) Int. Pat. Appl. WO 93/08174.
   Google Scholar
• NICHOLSON NS, TAITE B, PANZER-KNODLE S, SALYERS A, HAAS N, SZALONY J, ZABLOCKI JA, FEIGEN IP, GLENN K, ICELLER B, BROSCHAT K, HERIN M, JACQMIN P, LESNE M: An orally active glycoprotein fib-ma antagonist -SC-54684. Thromb. Haemostas. (1993) 69(6):a1558.
   Google Scholar
• FEIGEN LP, NICHOLSON NS, TAITE B, PANZER-KNODLE S, SALYERS A, HAAS N, SZALONY J, ZABLOCKI JA: Long-term
   Google Scholar
• Inhibition of platelets in dogs with the orally-active anb133 antagonist SC-54684. Thromb. Haemostas. (1993) 69(6):a1883.
   Google Scholar
• ZABLOCKI JA, NICHOISON NS, TAITE B, PANZER-KNODLE S, SALYERS A, HAAS N, SZALONY J, FEIGEN LP, HERIN M, JACQMIN P, LESNE M, BOVY P, TJOENG FS: Selection of an orally active glycoprotein Ilb/Illa receptor antago-nist for clinical trials. Thromb. Haemostas. (1993) 69(6):a2503.
   Google Scholar
• ZABLOCKI JA, BOVY PR, RICO JG, ROGERS TE, LINDMARK RJ, TJOENG FS, GARLAND RB, WILLIAMS K, SCHRETZMAN L, TOTH MV, McMACKINS DE, NICHOLSON NS, TAITE BB, PANZER-KNODLE SG, SALYERS AK, HAAS NF, SZALONY JA, RAO SN, MARKOS CS, FEIGEN LP: Potent in vitro and in vivo inhibitors of platelet aggregation based upon the arg-giy-asp sequence of fibrinogen. 207th ACS Meet-ing, San Diego, Medi - 14, Mar. 13th, 1994.
   Google Scholar
• DUGGAN ME, IHLE NC; European Patent 0478362 A, Apr 01, 1992.
   Google Scholar
• GOULD RJ, BARRETT JS, ELISS JD, HOLAHAN MA, S-11tA-NIERI MT, THEOHARIDES AD, LYNCH JJ, FRIEDMAN PA, DUGGAN ME, IHLE NC, ANDERSON PS, HARTMAN GD: Characterization of L-703,014, a novel fibrinogen recep-tor antagonist, following oral administration to dogs. Thromb. Haemostas. (1993) 69(6):a2.
   PubMedGoogle Scholar
• EGBERTSON MS, CHANG CT-C, DUGGAN ME, GOULD RJ, HALCZENKO W, HARTMAN GD, LASWELL WL, LYNCH RJ, MANNO PD, NAYLOR AM, PRUGH JD, RAMJIT DR, SITKO GR, SMITH RS, TURCHI LM, ZHANG G: Non-peptide fi-brinogen receptor antagonists. 2. Optimization of a tyrosine template as a mimic for arg-gly-asp. 207th ACS Meeting, San Diego, Medi - 15, Mar. 13th, 1994.
   Google Scholar
• EGBERTSON MS, NAYLOR AM, HARTMAN GD, COOK JJ, GOULD RJ, HOLAHAN MA, LYNCH Jr. JJ, LYNCH RJ, S1KA-NIERI MT, TURCHI LM: Non-peptide fibrinogen receptor antagonists. 3. Design and discovery of a centrally constrained inhibitor. 207th ACS Meeting, San Diego, Medi - 16, Mar. 13th, 1994.
   Google Scholar
• DUGGAN ME, IHLE N, HARTMAN G, TURCHI LM, EGBERT- SON MS, HOFFMAN WF: European Patent 512831-Al, Nov. 11, 1992.
   Google Scholar
• An interesting patent which contains potent confonnationally con-strained inhibitors of platelet aggregation.
   Google Scholar
• FOSTER MR, PIKE NB, HORNBY EJ, PORTER B, ELDRED CD, ROSS BC, LUMLEY P: 6R144053, a potent and specific non-peptide fibrinogen receptor antagonist on human platelets in vitro. Thromb. Haemostas. (1993) 69(6):a64.
   PubMedGoogle Scholar
• PIKE NB, FOSTER MR, HORNBY EJ, LUMLEY P: Effect of the fibrinogen receptor antagonist GR144053 upon platelet aggregation ex vivo following intravenous and oral administration to the marmoset and cynomolgus monkey. Thromb. Haemostas. (1993) 69(6):a1886.
   Google Scholar
• WHITE BP, LUMLEY P: GR144053, a fibrinogen receptor antagonist, prevents coronary thrombosis lathe anaes-thestised dog. Thromb. Haemostas. (1993) 69(6):a1886.
   Google Scholar
• AUSTEL V, EISERT WG, HIMMELSBACH F, LINZ G, MULLER TH, PIEPER H, SEEWALDT-BECKER E, WEISENBERGER H: Design of highly potent nonpeptidic fibrinogen recep-tor antagonists. 205th ACS Meeting, Denver, Medi - 101, Mar. 29th, 1993.
   Google Scholar
• MULLER TH, RUHR K, HIMMELSBACH F, SEEWALDT-BECKER E: The non-peptide fibrinogen receptor antago-nist BIBU 52, in contrast to aspirin, does not interfere with the modulation of thrombus formation by vascu-lar cells. Thromb. Haemostas. (1993) 69(6):a1888.
   Google Scholar
• MULLER TH, SCHURER H, WALDMANN L, BAUER E, HIM- MELSBACH F, BINDER K: Oral activity of BIBU 104, a prodrug of the non-peptide fibrinogen receptor antago-nist EMU 52, in mice and monkeys. Thromb. Haemostas. (1993) 69(6):a1557.
   Google Scholar
• This study documents the importance of screening compounds in several species, since BIBU 52 is rapidly cleared in dogs.
   Google Scholar
• MULLER TH, GERSTER U, KOCH V, HIMMELSBACH F, GUTH BD: BIBU 52, a non-peptide fibrinogen receptor antagonist, inhibits arterial thrombosis in vivo more effectively than either aspirin or heparin. Thromb. Haemostas. (1993) 69(6):a1889.
   Google Scholar
• BUSH LR, SHEBUSKI RJ: In vivo models of arterial tbrom- bosis and tbromolysis. FASEB (1990) 4:3087-3098. A good review of in vivo models.
   Google Scholar
• DEGRADO WF, JACKSON SA, MOUSA SA, PARTHASARATHY A, SWORIN M: World Patent 93/07170, April 15, 1993.
   Google Scholar
• MOUSA SA, DEGRADO WF, JACKSON SA, THOOLEN MJ, PIERCE SK, BOZARTH JM, HASSELL SM, REILLY TM: Anti-platelet efficacy and safety of the platelet GP Ilb/Ma antagonist, DMP 728 in anesthetized dogs. Circulation (1993) /38(4):II-a1706.
   Google Scholar
• During the authors' presentation, DMP 728 was stated to be orally active in dogs; however, to our knowledge, detailed data has not been disclosed.
   Google Scholar
• ROTE WE, MU D-X, MOUSA SA, REILLY TM, LUCCHESI BR: DMP728, a GP lib/Ma antagonist, enhances rt-PA-in-duced coronary thrombolysis and prevents rethrom-bosis in a chronic canine modeL Circulation (1993) 88(4):II-a2464.
   Google Scholar
• BERNARDI MM, CAUFF RM, ICLEIMAN N, ELUS SG, TOPOL EJ: Prolonged bleeding times do not predict hemorrhagic events in patients receiving the 7E3 glycoprotein fib/Ma platelet antibody. Circulation (1992) 86 (4):II-a1035.
   Google Scholar
• A statement was made in the conclusion of this presentation that a pro-rated 'dose of coadministered heparin based on weight of coad-ministered heparin may further diminish bleeding enhancement.
   Google Scholar
• MOUSA SA, BOZARTH JM, FORSYTHE MS, JACKSON MS, LEAMY A, DIEMER MM, KAPIL RP, KANBB RM, MAYO MC, PIERCE SK, DE GRADO WE, THOOLEN MJ, REILLY TM: Antiplatlet and antithrombotic efficacy of DMP 728, a novel platelet GP fib/ma receptor antagonist. Circula-tion (1994) 89:3–12.
   PubMed Web of Science ®Google Scholar
• HANDAGAMA P, SCARBOROUGH RM, SCHUMAN MA, BAINTON DF: Endocytosis of fibrinogen into inegakaryocytes and platelet a-granules is mediated by a11b03 (glycoprotein fib-H1a). Blood (1993) 82:135–138.
   PubMed Web of Science ®Google Scholar
• MOUSA SA, REILLY TM: Pharmacological blockade of platelet GP 11b/Ma and the inherited disorders of the platelet GP Ilb/Ma (Glanzmann's thrombasthenia): How safe is this antithrombotic approach for both acute and chronic treatment of thromboembolic disorders? Cardiology (1993) 83:36–37.
   PubMed Web of Science ®Google Scholar
• BENNETT JS, KOLODZIEJ MA: Disorders of platelet func-tion. Dir. Mon. (1992) 38:577–631.
   PubMedGoogle Scholar