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].
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.
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].
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].
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].
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].
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].
FXIa-IN-1 (compound EP-7041) is a potent β-lactam covalent heparin-derived factor XIa (fXIa) inhibitor[1].
Garadacimab (CSL312) is a first-in-class, fully human IgG4 monoclonal antibody targeting activated factor XII (FXIIa). Garadacimab has the potential for hereditary angioedema research[1].
Edoxaban (DU-176b) hydrochloride is an orally active, highly potent, selective, and direct Factor Xa (FXa) inhibitor with Ki values of 0.561 and 2.98 nM for free human FXa and prothrombinase. Edoxaban hydrochloride exhibits more than 10,000-fold selectivity over other coagulation proteases. Edoxaban hydrochloride can be used for preventing thromboembolic disease research[1].
FXIa-IN-8 is a potent and selective FXIa inhibitor with an IC50 of 14.2 nM. FXIa-IN-8 shows antithrombotic activity without increasing the bleeding risk and obvious toxicitysup>[1].
Frunexian (EP-7041) is a selective and potent inhibitor of coagulation factor XI/activated factor XI, targeting to factor XIa. Frunexian exhibits antithrombotic activity, with no bleeding liability in rat mesenteric arterial puncture model. Frunexian can be used in extracorporeal membrane oxygenation (ECMO) research[1].
Asundexian (BAY 2433334) is an orally active coagulation factor Xia (FXIa) inhibitor. Asundexian binds directly, potently, and reversibly to the active site of FXIa and thereby inhibits its activity. Asundexian inhibits human FXIa in buffer with an IC50 of 1 nM[1].
Ozagrel(OKY-046) sodium salt 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].
BMS-962212 is a direct, reversible, selective factor XIa (FXIa) inhibitor . BMS-962212 is well tolerated, with fast onset of pharmacodynamic (PD) responses and rapid elimination. BMS-962212 increases exposure dependently in activated partial thromboplastin time, and decreases exposure dependently in FXI clotting activity[1].
Otamixaban(FXV673) is a potent (Ki = 0.5 nM), selective, rapid acting, competitive and reversible fXa inhibitor that effectively inhibits both free and prothrombinase-bound fXa.IC50 value:Target: Factor Xa Otamixaban is a potent (Ki = 0.5 nM), selective, rapid acting, competitive and reversible fXa inhibitor that effectively inhibits both free and prothrombinase-bound fXa. In vivo experiments have demonstrated that Otamixaban is highly efficacious in rodent, canine and porcine models of thrombosis. In addition, recent clinical findings indicate that Otamixaban is efficacious, safe and well tolerated in humans and therefore has considerable potential for the treatment of acute coronary syndrome. This review article chronicles the discovery and pre-clinical data surrounding the fXa inhibitor Otamixaban as well as the recent clinical findings in humans.
Razaxaban hydrochloride (BMS 561389 hydrochloride) is a highly potent, selective and orally active factor Xa inhibitor with a Ki of 0.19 nM. Razaxaban hydrochloride exhibits excellent selectivity (>5000-fold) for factor Xa over other related serine proteases. Razaxaban hydrochloride is also a potent thrombin inhibitor with a Ki of 540 nM. Razaxaban hydrochloride has strongly antithrombotic activity[1].
Edoxaban-d6 is deuterium labeled Edoxaban. Edoxaban (DU-176) is a selective, potent and orally active factor Xa (FXa) inhibitor with Kis of 0.561 nM and 2.98 nM for free FXa and prothrombinase, respectively. Edoxaban is an anticoagulant agent and can be used for stroke prevention. Edoxaban is a also weak inhibitor of thrombin and factor IXaβ (FIXa), with Kis of 6.00 μM and 41.7 μM, respectively, exhibits >10 000-fold selectivity for FXa. Edoxaban has antithrombotic properties and has potential for thromboembolic diseases treatment[1][2][3].
Dechloro Rivaroxaban is a highly selective, orally active inhibitor of Factor Xa. Dechloro Rivaroxaban inhibits human free FXa with a Ki of 0.4 nM. Dechloro Rivaroxaban inhibits prothrombinase activity and fibrin-associated FXa activity with IC50s of 2.1 nM and 92 nM, respectively[1].
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].