Disease relevance of LY 294468

• Minor bleeding and thrombophlebitis occurred more frequently in the efegatran treated patients [1].
• Anticoagulant properties, clinical efficacy and safety of efegatran, a direct thrombin inhibitor, in patients with unstable angina [1].
• Both trials evaluated efegatran combined with thrombolysis for treating acute ST-segment elevation myocardial infarction (STEMI) [2].
• Efegatran was synthesized by the Hungarian Institute for Drug Research (IDR), which conducted phase II trials for angina in Hungary, and phase II trials for thrombosis in collaboration with Lilly in the US [182552] [3].

High impact information on LY 294468

• 7E3 alone and both combination treatments produced significant reductions in ADP, arachidonic acid, and thrombin-induced platelet aggregation, whereas efegatran and heparin abolished only thrombin-induced aggregation [4].
• Neither of the efegatran doses studied were able to suppress myocardial ischaemia during continuous ECG ischaemia monitoring to a greater extent than that seen with heparin [1].
• RESULTS: Efegatran demonstrated dose dependent ex-vivo anticoagulant activity with the highest dose level of 1.2 mg. kg(-1). h(-1)resulting in steady state mean activated partial thromboplastin time values of approximately three times baseline [1].
• The level of thrombin inhibition by efegatran, as measured by activated partial thromboplastin time, appeared to be more stable than with heparin [1].
• Major bleeding occurred in 23% of patients in the efegatran/streptokinase group versus 11% in the heparin/TPA group (P = not significant) [5].

Biological context of LY 294468

• The thrombin time (TT) assay was prolonged twofold with 33 nM Efegatran, which demonstrated an apparent Kass value of 0.8 x 10(8) L/mol (for comparison, 17 nM hirudin was required to prolong the TT assay two-fold) [6].
• The data suggest that LY287045, LY294291, and Efegatran should be expected to be useful as antithrombotic adjuncts to thrombolytic therapy with t-PA, urokinase, or streptokinase and should be expected to spare endogenous fibrinolysis [6].

Associations of LY 294468 with other chemical compounds

• The thrombin inhibitors argatroban, efegatran, NAPAP, CH 1091, CH 248, inogatran and melagatran have been characterised with respect to their mechanism of binding to human alpha-thrombin [7].

Gene context of LY 294468

• Increase in VE-cadherin-positive cells was inhibited by hirudin and efegatran [8].
• Outlined are the main projects and the most significant results, which include the first synthesis of human ACTH, the discovery of GYKI-14 166, the prototype of peptide inhibitors of thrombin, a stable anticoagulant, efegatran GYKI-14 766, and their dual acting analogues [9].

Analytical, diagnostic and therapeutic context of LY 294468

• This study was designed to compare the efficacy of efegatran plus streptokinase versus heparin plus accelerated tissue plasminogen activator (TPA) in coronary reperfusion in acute MI [5].

References