JTV-803
JTV-803 is a selective and competitive direct factor Xa (FXa) inhibitor with a Ki of 19 nM and an IC50 of 81 nM against human FXa, and its action is independent of antithrombin III (ATIII). JTV-803 exhibits significantly higher selectivity for human FXa than for thrombin, plasmin, and trypsin. JTV-803 produces sustained ex vivo anti-FXa inhibitory activity in vivo. JTV-803 prolongs aPTT and PT, prevents dialyzer thrombosis, and is cleared during dialysis. JTV-803 dose-dependently attenuates coagulation activation, maintains plasma ATIII activity, reduces glomerular fibrin deposition, and improves survival rate. JTV-803 can be used for research related to thrombosis and hemodialysis anticoagulation.
For research use only. We do not sell to patients.
- CAS No.: 247131-06-2
- Formula: C22H27N5O3
- Molecular Weight:409.48
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
In Vitro
JTV-803 (20 min) is a competitive inhibitor of purified human factor Xa with a Ki of 19 nM[1].
JTV-803 is a selective human factor Xa inhibitor, exhibiting greater than 100-fold selectivity over human thrombin, plasmin, and trypsin[1].
JTV-803 inhibits human and porcine factor Xa with low micromolar IC50 values (IC50 = 0.07 μM and 0.15 μM, respectively) [2].
JTV-803 (3693 ng/mL) doubles the APTT in human plasma[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
JTV-803 (0.3-3.0 mg/kg; intravenous injection; single administration; before TF injection) exhibits dose-dependent anti-DIC effects in TF-induced DIC in rats[3].
JTV-803 (0.3-3.0 mg/kg; intravenous injection; single administration; before LPS (HY-D1056) injection) dose-dependently ameliorates LPS-induced DIC in rats and completely prevents death[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male pigs (30.1-41.8 kg)[2]
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Dosage:0.3 mg/kg bolus + 1.0 mg/kg/h infusion; 0.3 mg/kg bolus + 3.0 mg/kg/h infusion; 0.3 mg/kg bolus + 0.3 mg/kg/h infusion
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Administration:Intra-arterial (dialysis circuit); bolus followed by continuous infusion
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Result:Prolonged dialysis time to 201 min at 0.3 mg/kg + 1.0 mg/kg/h and 239 min at 0.3 mg/kg + 3.0 mg/kg/h, compared to 123 min in vehicle group.
Prevented thrombus formation in dialyzers.
Prolonged prothrombin time by 2-fold or more after 4 h at 0.3 mg/kg + 3.0 mg/kg/h.
Prolonged prothrombin time by 1.5-fold or less after 4 h at 0.3 mg/kg + 1.0 mg/kg/h.
Achieved in vivo plasma concentration of 2795 ng/mL at 0.3 mg/kg + 3.0 mg/kg/h and 463 ng/mL at 0.3 mg/kg + 1.0 mg/kg/h after 4 h.
Showed positive correlation between prothrombin time prolongation and plasma concentration.
Clearance rate was 53.4-80.0% at 0.3 mg/kg + 0.3 mg/kg/h, 62.8-81.8% at 0.3 mg/kg + 1.0 mg/kg/h, and 70.9-80.3% at 0.3 mg/kg + 3.0 mg/kg/h.
Decreased plasma concentration from 2795 ng/mL to 885 ng/mL at 1 h after end of dialysis at 0.3 mg/kg + 3.0 mg/kg/h.
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Animal Model:Wistar (Male, 6-7 weeks old, 160-170 g)[3]
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Dosage:0.3 mg/kg (bolus i.v., single dose prior to TF injection); 3.0 mg/kg (bolus i.v., single dose prior to TF injection)
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Administration:i.v.; single dose; prior to TF injection
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Result:In the TF-induced DIC model, this compound at 0.3 mg/kg resulted in platelet count (PLT) of 416 x 109/l, PT of 22.6 s, fibrinogen of 117.3 mg/dl, D-dimer of 2.5 μg/mL, TAT of 48.6 ng/mL, ATIII of 85.6%, creatinine of 0.16 mg/dl, ALT of 53.2 U/l, and %GFD of 24.2%.
This compound at 3.0 mg/kg resulted in PLT of 572 x 109/l, PT of 16.0 s, fibrinogen of 241.6 mg/dl, D-dimer of 0.1 μg/mL, TAT of 9.2 ng/mL, ATIII of 93.8%, creatinine of 0.14 mg/dl, ALT of 54.3 U/l, and %GFD of 6.8%.
The effect of this compound on DIC induced by TF was dose dependent.
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Animal Model:Wistar (Male, 6-7 weeks old, 160-170 g)[3]
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Dosage:0.3 mg/kg (bolus i.v., single dose prior to LPS (HY-D1056) injection); 3.0 mg/kg (bolus i.v., single dose prior to LPS injection)
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Administration:i.v.; single dose; prior to LPS injection
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Result:In the LPS-induced DIC model, none of the 20 rats treated with this compound (0.3 and 3.0 mg/kg) died, compared to 7 of 22 untreated rats (mortality 31.8%) and 6 of 16 LMWH-treated rats (mortality 37.5%).
This compound at 0.3 mg/kg resulted in PLT of 189 x 109/l, fibrinogen <50.0 mg/dl, D-dimer of 1.1 μg/mL, TAT of 120.5 ng/mL, ATIII of 61.2%, creatinine of 0.31 mg/dl, ALT of 72.2 U/l, and %GFD of 76.7%.
This compound at 3.0 mg/kg resulted in PLT of 190 x 109/l, PT of 38.3 s, fibrinogen of 78.4 mg/dl, D-dimer of 0.9 μg/mL, TAT of 102.6 ng/mL, ATIII of 80.4%, creatinine of 0.24 mg/dl, ALT of 68.7 U/l, and %GFD of 45.0%.
DIC (except for Plts) significantly improved after treatment with both doses of this compound, and the effect was dose dependent.
ATIII was more preserved in the group treated with this compound (3.0 mg/kg) than with LMWH.
Chemical Information
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CAS No. 247131-06-2
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Molecular Weight 409.48
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Formula C22H27N5O3
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SMILES
O=C(C1(CCN(CC1)C2=CC=NC=C2)COC3=CC=C4C(CN(CC4)C(N)=N)=C3)O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
JTV-803 Related Classifications
HY-187960 Related Classifications
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