thrombin inhibitor 1

Thrombin inhibitor 1 is a potent inhibitor of thrombin [Ki: 0.66 nM, 2xaPTT=0.43 μM].

Thrombin inhibitor 13 (Compound 13a) acts as a covalent reversible inhibitor of thrombin (thrombin, FIIa) with an IC50 of 0.7 nM. This compound prolongs activated partial thromboplastin time (aPTT) and prothrombin time (PT), demonstrating both antithrombotic and anticoagulant properties.

Atopaxar (E5555), a reversible PAR-1 thrombin receptor antagonist, interferes with platelet signaling. Atopaxar has been investigated for the treatment of Coronary Artery Disease and Acute Coronary Syndrome.

Edoxaban (Lixiana) (DU-176) is a selective, potent and orally active factor Xa (FXa) inhibitor with K i s of 0.561 nM and 2.98 nM for free FXa and prothrombinase, respectively. Edoxaban is an anticoagulant agent and is able to be used for stroke prevention. Edoxaban is a also weak inhibitor of thrombin and factor IXaβ (FIXa), with K i s of 6.00 μM and 41.7 μM, respectively, exhibits >10 000-fold selectivity for FXa. Edoxaban has antithrombotic properties and is potential for thromboembolic diseases treatment [1] [2] [3].

Patamostat (E-3123) is a potent protease inhibitor that effectively inhibits trypsin, plasmin, and thrombin with IC50 values of 39 nM, 950 nM, and 1.9 µM, respectively. Research suggests it might suppress the pathogenesis and development of acute pancreatitis [1] [2].

Parmodulin 2 (ML 161) is the inhibitor of protease-activated receptor 1 (PAR1)-mediated platelet activation (IC50: 0.26 μM for the inhibition of platelet P-selectin expression on human platelets). It also inhibits thrombin-induced platelet activation.

Atopaxar, a reversible PAR-1 thrombin receptor antagonist, interferes with platelet signaling. Atopaxar has been investigated for the treatment of Coronary Artery Disease and Acute Coronary Syndrome.

Bivalirudin (BG-8967) is a reversible inhibitor of α- and ζ-thrombin (Kis = 2.56 and 1.84 nM, respectively), enzymes that exhibit high fibrinogen-clotting activities.

Vorapaxar (MK-5348) (SCH 530348) is an effective and orally active thrombin receptor (PAR-1) antagonist (Ki: 8.1 nM).

SCH79797 dihydrochloride is an effective and selective antagonist of protease activated receptor 1 (PAR1) with an IC50 of 70 nM and a Ki of 35 nM. SCH79797 dihydrochloride has antiproliferative and pro-apoptotic effects.

Thrombin inhibitor 5 (compound 385) is a thrombin inhibitor with IC50 values ranging from 0.1 μM to 1 μM, suitable for venous thromboembolism research[1].

C1s-IN-1 trihydrochloride (Compound A1) is a selective inhibitor of C1s protease with a Ki of 5.8 μM. This compound inhibits the cleavage of C2 by C1s with an IC50 of 85 μM and prevents activation of the classical pathway, with an IC50 of 22 μM. Additionally, C1s-IN-1 trihydrochloride acts as a competitive inhibitor of thrombin, exhibiting a Ki of 51.2 μM.

Vorapaxar sulfate (Zontivity) is a potent and orally active thrombin receptor (PAR-1) antagonist.

RWJ-56110 dihydrochloride is a potent, selective, peptide-mimetic inhibitor of PAR-1 activation and internalization (binding IC50=0.44 μM), showing no effect on PAR-2, PAR-3, or PAR-4. It inhibits the aggregation of human platelets induced by SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM), with high selectivity relative to U46619. RWJ-56110 dihydrochloride also blocks angiogenesis and the formation of new vessels in vivo, and induces cell apoptosis[1][2].

Thrombin receptor agonist peptide (TRAP-14) is a 14-amino acid peptide agonist of the α-thrombin receptor. It induces aggregation of washed platelets as well as platelets in citrated and hirudin plasma. TRAP-14 (100 μM) increases the cytosolic calcium concentration in isolated guinea pig pulmonary smooth muscle cells 5-fold over baseline. It increases pulmonary arterial pressure in isolated guinea pig lung when used at a concentration of 1 μM, which is comparable to the effect induced by 10 nM α-thrombin. TRAP-14 also induces contraction of isolated rat aortic rings and increases endothelin-1 (ET-1) levels in a dose-dependent manner, an effect that is reversed by the ETA antagonist BQ-123 and the nitric oxide synthase (NOS) inhibitor L-NNA .

Thrombin Inhibitor 6, with an IC 50 of 1 nM, acts as a potent anticoagulant by inhibiting thrombin.

Lepirudin, a recombinant form of hirudin, serves as a potent, irreversible inhibitor of thrombin, showcasing its anticoagulant efficacy in heparin-induced thrombocytopenia (HIT) [1].

Bivalirudin TFA, a synthetic 20-residue peptide, serves as a reversible inhibitor of thrombin. Its IC50 value highlights its target specificity in vitro, where, combined with Eptifibatide (8 mg mL) at a low concentration (70 ng mL), it significantly reduces platelet aggregation induced by thrombin (0.2 U mL) by approximately 90% [1]. The compound demonstrates no effect on thrombin generation assay (TGA) parameters up to 10 μmol L [2]. Additionally, it facilitates the binding of MPO to BAEC, leading to functional alterations such as increased NO consumption and enhanced MPO-mediated redox modifications [3]. In vivo studies reveal its efficacy in preventing the rise of antiheparin PF4 antibody IgG levels in rats, with significant findings from the toxicokinetic assessment signaling its safety profile at tested doses, although higher doses resulted in fatalities [4][5]. In clinical trials, its antithrombotic effects were explored, comparing it with alternatives like Ticagrelor and Clopidogrel in a Phase 4 study.

Benzenecarboximidamide, hydrochloride, hydrate (1:1:x) (Benzamidine hydrochloride hydrate) is a reversible competitive trypsin-like serine proteases inhibitor with K i s of 20, 21, 97, 110, 320 and 750 μM against Tryptase, Trypsin, uPA, Factor Xa , Thrombin and tPA, respectively [1] [2] .

Pyr-Arg-Thr-Lys-Arg-AMC TFA, an AMC-tagged decapeptide, is selectively cleaved by proteases such as trypsin and thrombin, serving as a substrate for measuring protease activity and assessing enzyme inhibitor efficacy [1].

Hirullin P18, a potent thrombin inhibitor with anticoagulant properties [1].

Z-FK-ck (Z-Phe-Lys-2,4,6-Trimethylbenzoyloxy-methylketone) is a potent and selective inhibitor of gingipain-K, effectively extending plasma thrombin time (TT) in proportion to dosage and duration [1].

Glycylglycylcysteine is an inhibitor of Thrombin Activatable Fibrinolysis Inhibitor (TAFI), exhibiting a K_i value of 0.99 µM and an IC_50 of 9.4 µM in TAFI substrate assays. TAFI, a basic carboxypeptidase, hinders fibrinolysis by cleaving C-terminal lysine residues on partially degraded fibrin [1].

SAR107375 is a potent, orally active dual inhibitor of thrombin and factor Xa, with K_i values of 1 nM and 8 nM for factor Xa and thrombin, respectively [1].