Characteristics of the hemostatic action of KFA-1411, an inhibitor of coagulation factor Xa (FXa), in humans and various animals.

  title={Characteristics of the hemostatic action of KFA-1411, an inhibitor of coagulation factor Xa (FXa), in humans and various animals.},
  author={Kiyoto Hara and Toshiki Honma and Akane Matsuzawa and Atsushi Matsuzawa and Masahiko Uchida and Takashi Koizumi and Satoshi Akahane and Masami Kojima},
  journal={The Journal of toxicological sciences},
  volume={28 1},
  • K. Hara, T. Honma, +5 authors M. Kojima
  • Published 28 February 2003
  • Chemistry, Medicine
  • The Journal of toxicological sciences
This study examined a low-molecular-weight factor-Xa inhibitor, KFA-1411 (3-[N-(3-amidinophenyl)-N-[N-[4-[1-(1-iminoethyl)piperidin-4- yl]phenyl]carbamoylmethyl]aminomethyl]phenoxyacetic acid monosulfonate-dihydrate). KFA-1411 selectively inhibited FXa among the serine proteases in the human blood-coagulation cascade with a Ki value of 1.73 nM, (selectivity ratio, 15000 versus its action on thrombin). The anticoagulant action of KFA-1411 in human plasma almost equaled that of the selective… Expand
Factor Xa inhibitors: new anti-thrombotic agents and their characteristics.
Synthetic, selective, and direct inhibitors to FXa, such as DX-9065a, are highly potent and orally bioavailable antithrombotic agents that have demonstrated an improved side effect profile, probably by allowing sufficient thrombin to remain for platelet activation and normal hemostasis, while preventing pathological thrombus formation. Expand
Orally active factor Xa inhibitors: investigation of a novel series of 3-amidinophenylsulfonamide derivatives using an amidoxime prodrug strategy.
A series of novel and potent 3-amidinophenylsulfonamide derivatives of factor Xa inhibitors were designed and synthesized using an amidoxime prodrug strategy, and KFA-1982 was selected for clinical development. Expand
Novel Sulfated 4-Hydroxycinnamic Acid Oligomers as Potent Anticoagulants
NOVEL SULFATED 4-HYDROXYCINNAMIC ACID OLIGOMERS AS POTENT ANTICOAGULANTS By Brian Lawrence Henry, Ph.D. A Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor ofExpand


Species differences in anticoagulant and anti-Xa activity of DX-9065a, a highly selective factor Xa inhibitor.
The inhibitory effect of DX-9065a on FXa from several animal species and its anticoagulant effect ex vivo in these species are examined and compared with that of NAPAP, a benzamidine-derived direct thrombin inhibitor. Expand
DX-9065a, a new synthetic, potent anticoagulant and selective inhibitor for factor Xa.
The results suggest that DX-9065a may become an anticoagulant by means of the specific inhibition of factor Xa. Expand
Comparison of sustained antithrombotic effects of inhibitors of thrombin and factor Xa in experimental thrombosis.
CVS#995 was shown to also enhance the extent of endogenous fibrinolysis to a greater degree compared with rHir and might therefore be an interesting new antithrombotic agent for the treatment of venous and arterial thrombosis. Expand
Sustained inhibition of whole-blood clot procoagulant activity by inhibition of thrombus-associated factor Xa.
Uninhibited thrombus-associated Xa activity may account for the increases in thrombin activity that are commonly observed in clinical trials after discontinuation ofThrombin inhibitors. Expand
Analysis of the generation and inhibition of activated coagulation factor X in pure systems and in human plasma.
  • J. Jesty
  • Biology, Medicine
  • The Journal of biological chemistry
  • 1986
In plasma, factor Xa generated in the presence of phospholipid and Ca2+ ions by RVV-X, factor IXa, or tissue factor was inhibited more slowly than exogenous enzyme, and protection by tissue factor activation was also observed in pure systems and apparently required factor VII. Expand
DX 9065A a novel, synthetic, selective and orally active inhibitor of factor Xa: in vitro and in vivo studies.
Compared to standard heparin, DX 9065A exhibited a favorable antithrombotic/bleeding ratio, therefore showing that it might be considered as a promising compound in the treatment and prevention of various thrombosis diseases. Expand
Synthesis of thrombin-inhibiting heparin mimetics without side effects
The use of multistep converging synthesis to obtain sulphated oligosaccharides that meet the requirements of more potent and well-tolerated antithrombotic drugs is described. Expand
Crystallographic analysis of potent and selective factor Xa inhibitors complexed to bovine trypsin.
A number of factor Xa inhibitors were crystallographically studied complexed to bovine trypsin and bear a resemblance to the reported binding mode of DX-9065a in bovines trypsIn and humanfactor Xa. Expand
Anticoagulant activities and effects on platelets of a heparin fragment with high affinity for antithrombin.
The molecular weight of the heparin was found to be the most important factor determining the platelet aggregation activity, low molecular weight fractions including the fragment being much less active than high molecular weight ones. Expand
Anticoagulant activities of heparin oligosaccharides and their neutralization by platelet factor 4.
An octadecasaccharide is therefore the smallest heparin fragment that can accelerate thrombin inhibition by antithrombin III, and was more readily neutralized by platelet factor 4 than were their anti-Factor Xa activities. Expand