Edoxaban(DU-176) is an oral factor Xa (FXa) inhibitor in clinical development for stroke preventionIC50 Value:Target: factor XaEdoxaban is an oral factor Xa (FXa) inhibitor in clinical development for stroke prevention in patients with atrial fibrillation, an elderly population that frequently receives aspirin (ASA) and/or nonsteroidal anti-inflammatory drugs for concurrent illnesses[1].in vitro: Edoxaban PK was not affected by concomitant low-dose ASA or naproxen, but high-dose ASA increased systemic exposure of edoxaban by approximately 30%. The effects of edoxaban on prothrombin time, activated partial thromboplastin time, international normalized ratio, anti-FXa, and intrinsic FXa activity were not influenced by administration with ASA or naproxen. Inhibition of platelet aggregation by high-dose ASA, low-dose ASA, or naproxen was not affected by edoxaban[1].in vivo: Forty-eight subjects, aged 18 to 45 years, received either edoxaban 60 mg once daily × 7 days (n = 24) or digoxin 0.25 mg twice daily × 2 days and once daily × 5 days (n = 24) and then concomitantly for 7 days. Serial blood and urine samples were collected for digoxin and edoxaban concentrations on days 7 and 14. Serial coagulation assays were measured for edoxaban on days 7 and 14. Edoxaban PK parameters demonstrated mild increases in area under the curve and peak concentrations of 9.5% and 15.6%, respectively[2],Clinical trial: Pharmacokinetics, biotransformation, and mass balance of edoxaban, a selective, direct factor Xa inhibitor, in humans was reported[3].
Enoxaparin (PK 10169), a low-molecular-weight heparin (LMWH) derivative. Enoxaparin exerts anticoagulant activity through antithrombin III, an endogenous inhibitor of factor Xa and thrombin IIa. Enoxaparin protect the rat hippocampus against TBI (traumatic brain injury) via antioxidant and anti-inflammatory properties. Enoxaparin can be used for the research of deep vein thrombosis (DVT), pulmonary embolism, TBI and COVID-19[1][2][3].
Fitusiran (ALN-AT3SC), an small interfering RNA, specifically targets antithrombin (AT) messenger RNA to lower production of AT in the liver. Fitusiran increases thrombin generation and has the potential for the research of the hemophilia[1].
Betrixaban (PRT054021) hydrochloride is a highly potent, selective, and orally efficacious factor Xa (fXa) inhibitor with an IC50 of 1.5 nM. Betrixaban hydrochloride shows antithrombotic effect[1][3].
FXa-IN-1 is a FXa inhibitor (IC50: 3 nM, Ki: 0.7 nM) with respectable oral bioavailability and half-life in vivo. FXa-IN-1 can be used for thromboembolic disorders[1].
FXIa-IN-7 is a selective and orally bioavailable factor XIa inhibitor with an IC50 value of 0.4 nM.
Osocimab (BAY 1213790), an anti-FXIa antibody (Ki=2.4 nM; EC50=0.2 nM). FXI inhibition may reduce the risk of thrombosis. Osocimab inhibits thrombin generation, and prolongs activated partial thromboplastin time. Osocimab exhibits anticoagulant effects[1].
5-R-Rivaroxaban is (R)-enantiomer of Rivaroxaban. Rivaroxaban (BAY 59-7939) is a highly potent and selective, direct Factor Xa (FXa) inhibitor, achieving a strong gain in anti-FXa potency (IC50 0.7 nM; Ki 0.4 nM).
Otamixaban (FXV673) is a potent, selective, rapid-acting, competitive, and reversible fXa inhibitor (Ki=0.5 nM) that effectively inhibits both free and prothrombinase-bound fXa[1].
Gabexate Mesylate is a Factor X inhibitor; serine protease inhibitor .Target: Factor XGabexate mesylate is a non-antigenic synthetic inhibitor of trypsin-like serine proteinases that is therapeutically used in the treatment of pancreatitis and disseminated intravascular coagulation and as a regional anticoagulant for hemodialysis. Values of the inhibition constant (K(i)) for gabexate mesylate binding to human and bovine tryptase were 3.4 x 10(-9) M and 1.8 x 10(-7) M (at pH 7.4 and 37.0 degrees ), respectively. Gabexate mesylate inhibited the fibrinogenolytic activity of human tryptase [1]. Gabexate Mesylate decreased the TNFalpha production of LPS-stimulated monocytes as shown by the inhibition of mRNA expression and increased the IL-10 production of LPS-stimulated monocytes. Gabexate Mesylate also suppressed the NFkappaB activity of LPS-stimulated monocytes. Inhibitory effect of Gabexate Mesylate on the TNFalpha production of activated human monocytes is mediated by the suppression of NFkappaB activation [2]. Gabexate mesylate inhibits competitively constitutive and inducible NO synthase (cNOS and iNOS, respectively), with Kivalues of 1.0×10?4M and 5.0×10?3M, respectively, at pH 7.4 and 37.0°C. gabexate mesylate increases iNOS mRNA expression in rat C6 glioma cells, as induced byE. colilipopolysaccharide plus interferon-γ. Gabexate mesylate inhibits dose-dependently nitrite production (i.e. NO release) in rat C6 glioma cells, as induced byE. colilipopolysaccharide plus interferon-γ [3].
Rivaroxaban D4 (BAY 59-7939 D4) is a deuterium labeled Rivaroxaban. Rivaroxaban is a highly potent，selective and direct Factor Xa (FXa) inhibitor, achieving a strong gain in anti-FXa potency (IC50 0.7 nM; Ki 0.4 nM)[1][2].
FXIa-IN-13 (example 1) is an Factor Xa inhibitor with antithrombotic activity. FXIa-IN-13 inhibits arteriovenous thrombosis in vivo and in vitro[1].
EMD 495235 is a potent and orally active coagulation factor Xa inhibitor with an IC50 of 5.5 nM and a Ki of 6.8 nM. EMD 495235 shows anticoagulant activities[1].
Betrixaban is a highly potent, selective, and orally efficacious factor Xa (fXa) inhibitor with IC50 of 1.5 nM.
BMS-262084 is a potent, selective and irreversible inhibitor of factor XIa, with an IC50 of 2.8 nM against human factor XIa. BMS-262084 also inhibits human tryptase (IC50=5 nM). BMS-262084 exhibits antithrombotic effects[1][2].
Apixaban 13CD3 (BMS-562247-01 13CD3) is a deuterium labeled Apixaban. Apixaban is a highly selective, reversible inhibitor of Factor Xa with Ki of 0.08 nM and 0.17 nM in human and rabbit, respectively[1].
RWJ-445167 is a dual inhibitor of thrombin and factor Xa with Ki of 4.0 nM and 230 nM, respectively, exhibiting potent antithrombotic activity.
Zifaxaban is a novel, potent, selective, direct and oral factor Xa inhibitor with IC50 of 11.1 nM (human FXa), displays > 10,000-fold selectivity than other serine proteases; also deoes not impair platelet aggregation induced by collagen, adenosine diphosphate (ADP) or arachidonic acid; significantly prolongs clotting time, prothrombin time (PT), and activated partial thromboplastin time (APTT) in the plasma of humans, rabbits, and rats, with a relatively weak effect on thrombin time; strongly suppresses thrombus formation with ED50 values of 3.09 mg/kg in venous thrombosis models in rats.
BMS-654457 is a small-molecule, reversible inhibitor of factor XIa (FXIa), binding with human and rabbit FXIa with Kis of 0.2 and 0.42 nM, respectively.
Darexaban (YM150) is a potent, selective and orally active factor Xa (FXa) inhibitor with an IC50 of 54.6 nM. Darexaban shows high selectivity against other related serine proteases, such as trypsin, thrombin, and kallikrein. Darexaban has anticoagulant and antithrombotic effects[1][2][3].
Ozagrel(OKY-046) is an antiplatelet agent working as a thromboxane A2 synthesis inhibitor.Target: Thromboxane A2 SynthaseOzagrel was selected as the best compound of highly selective inhibitors of TXA2 synthase. The inhibition of TXA2 synthase by ozagrel was more effective on human and rabbit enzymes than those of other species. Ozagrel increased 6-keto-PGF1 alpha, one of stable metabolites of PGI2, in various isolated cells and tissues perhaps via accumulated PG endoperoxides resulted by the inhibition of TXA2 synthase [1]. Ozagrel was estimated to be a reversible mixed-type inhibitor of diphenolase activity with the constants (K (S1), K (S2), K (i1), and K (i2)) determined to be 2.21, 3.89, 0.454, and 0.799 mM, repectively [2]. Infusion of OKY-046 significantly inhibited pulmonary thromboxane B2 delivery, attenuated the early increase in pulmonary vascular resistance, and blocked the increase in systemic vascular resistance. In addition, OKY-046 blunted and delayed the decrease in cardiac output and maintained end-systolic pressure-diameter relation, +dp/dt, and lung lymph flow at baseline values [3].
Methoxycarbonyl-D-Nle-Gly-Arg-pNA is a synthetic trypsin that can serve as a substrate for coagulation factors IXa (FIXa) and Xa (FXa)[1][2][3].
Denecimig (Mim8) is a novel activated coagulation factor VIII-mimetic human bispecific antibody with anti-FIXa and anti-FX arms that potently stimulates FX activation resulting in efficacious haemostasis in vitro and in vivo[1].
Fondaparinux sodium is an antithrombin-dependent factor Xa inhibitor.
Apixaban is a highly selective, reversible inhibitor of Factor Xa with Ki of 0.08 nM and 0.17 nM in human and rabbit, respectively.
D-Pro-Phe-Arg-Chloromethylketone, a inhibitor of coagulation factor XII and plasma kallikrein, plays an important role in thrombosis and inflammation[1].
LY-517717 is a potent and orally active FXa inhibitor. LY-517717 shows antithrombotic and anticoagulant activity. LY-517717 has the potential for the research of venous thromboembolism after hip or knee replacement[1].
Milvexian (BMS-986177), an effective antithrombotic agent, is an orally-bioavailable, reversible and direct inhibitor of human and rabbit factor XIa (FXIa) with Ki of 0.11, and 0.38 nM, respectively[1].
CH3OCO-D-CHA-Gly-Arg-pNA acetate is a chromogenic substrate for factor Xa[1][2].
Abelacimab (MAA868) is a fully human IgG1 monoclonal antibody that binds with high affinity to the catalytic structural domain of FXI and locks it in the zymogen conformation, thereby preventing its activation by FXIIa or thrombin. Abelacimab can be used in thromboembolic disease studies[1][2].