产品
编 号：F756130
分子式：C23H18Cl2F3N9O2
分子量：580.35
分子式：C23H18Cl2F3N9O2
分子量：580.35
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规格
价格
是否有货
结构图
CAS No: 2816108-87-7
产品详情
生物活性：
FXIa-IN-9 (compound 3f) is a potent and selective FXIa inhibitor. FXIa-IN-9 can bind with FXIa and form hydrogen bond (human FXIa Ki: 0.17 nM, rabbit FXIa Ki: 0.5 nM). FXIa-IN-9 also has anticoagulant activity, and can be used in the research of thromboembolic diseases such as atrial fibrillation, stroke, myocardial infarction, deep vein thrombosis, and pulmonary embolism.
体内研究：
FXIa-IN-9 (marginal ear intravenous injection, 1.7-10 mg/kg, dosing at 20 min prior to and 40 min during the AV shunt) achieves more than 50% thrombus reduction in the rabbit arteriovenous (AV) shunt thrombosis model.FXIa-IN-9 (i.v. or p.o., 1-10 mpk ) shows low clearance in rat and dog and moderate clearance in the monkey as well as good oral bioavailability.Animal Model:Rabbit AV shunt thrombosis model
Dosage:1.7 mg/kg bolus + 2.0 mg/kg/h infusion, or 8.5 mg/kg bolus + 10 mg/kg/h infusion.
Administration:Intravenous dosing via the marginal ear vein 20 min prior to and 40 min during the AV shunt
Result:Showed 36.5% (1.7 mg/kg bolus + 2.0 mg/kg/h infusion) and 62.2% (8.5 mg/kg bolus + 10 mg/kg/h infusion) inhibitions in thrombus weight, respectively.
Animal Model:Rat, dog, monkey (pharmacokinetic assay)
Dosage:1 mpk, 2 mpk (i.v.); 5 mpk, 10 mpk (p.o.)
Administration:Intravenous injection, oral administration.
Result:Pharmacokinetic profile of FXIa-IN-9 in kinds of species.animal speciesclearance (mL/min/kg)T1/2 (h)Vdss (L/kg)F%AUC (iv) (μM?h)AUC (po) (μM?h)Dose iv/po (mpk)
rat10.71.40.836.45.510.02/10
dog7.92.01.580.53.714.71/5
monkey25.61.01.543.01.12.51/5
体外研究：
FXIa-IN-9 has anticoagulant activity, with EC1.5x values of 1.31 μM (human plasma aPTT) and 1.39 μM (rabbit plasma aPTT), respectively.FXIa-IN-9 (10 μM, 5-15 min) is highly selective for FXIa against other human serine protease, except for plasma kallikrein (IC50: 0.023 μM).FXIa-IN-9 shows the plasma protein binding ranges from 80.8 to 95.6%, and pharmacological profile is as follows.property/assayvalue
equilibrium solubility (pH 1.2; pH 6.8)81.0 μM; 171.6 μM
PPB % (mouse/rat/dog/human)91.2/91.6/80.8/95.6
hERG inhibition (IC50)>10 μM
S9 aldehyde oxidase (AO) T1/2 > 180 min
hLM trapping assayno GSH and CN adducts
AMES genotoxicity testnegative
in vitro micronucleus testnegative
FXIa-IN-9 (compound 3f) is a potent and selective FXIa inhibitor. FXIa-IN-9 can bind with FXIa and form hydrogen bond (human FXIa Ki: 0.17 nM, rabbit FXIa Ki: 0.5 nM). FXIa-IN-9 also has anticoagulant activity, and can be used in the research of thromboembolic diseases such as atrial fibrillation, stroke, myocardial infarction, deep vein thrombosis, and pulmonary embolism.
体内研究：
FXIa-IN-9 (marginal ear intravenous injection, 1.7-10 mg/kg, dosing at 20 min prior to and 40 min during the AV shunt) achieves more than 50% thrombus reduction in the rabbit arteriovenous (AV) shunt thrombosis model.FXIa-IN-9 (i.v. or p.o., 1-10 mpk ) shows low clearance in rat and dog and moderate clearance in the monkey as well as good oral bioavailability.Animal Model:Rabbit AV shunt thrombosis model
Dosage:1.7 mg/kg bolus + 2.0 mg/kg/h infusion, or 8.5 mg/kg bolus + 10 mg/kg/h infusion.
Administration:Intravenous dosing via the marginal ear vein 20 min prior to and 40 min during the AV shunt
Result:Showed 36.5% (1.7 mg/kg bolus + 2.0 mg/kg/h infusion) and 62.2% (8.5 mg/kg bolus + 10 mg/kg/h infusion) inhibitions in thrombus weight, respectively.
Animal Model:Rat, dog, monkey (pharmacokinetic assay)
Dosage:1 mpk, 2 mpk (i.v.); 5 mpk, 10 mpk (p.o.)
Administration:Intravenous injection, oral administration.
Result:Pharmacokinetic profile of FXIa-IN-9 in kinds of species.animal speciesclearance (mL/min/kg)T1/2 (h)Vdss (L/kg)F%AUC (iv) (μM?h)AUC (po) (μM?h)Dose iv/po (mpk)
rat10.71.40.836.45.510.02/10
dog7.92.01.580.53.714.71/5
monkey25.61.01.543.01.12.51/5
体外研究：
FXIa-IN-9 has anticoagulant activity, with EC1.5x values of 1.31 μM (human plasma aPTT) and 1.39 μM (rabbit plasma aPTT), respectively.FXIa-IN-9 (10 μM, 5-15 min) is highly selective for FXIa against other human serine protease, except for plasma kallikrein (IC50: 0.023 μM).FXIa-IN-9 shows the plasma protein binding ranges from 80.8 to 95.6%, and pharmacological profile is as follows.property/assayvalue
equilibrium solubility (pH 1.2; pH 6.8)81.0 μM; 171.6 μM
PPB % (mouse/rat/dog/human)91.2/91.6/80.8/95.6
hERG inhibition (IC50)>10 μM
S9 aldehyde oxidase (AO) T1/2 > 180 min
hLM trapping assayno GSH and CN adducts
AMES genotoxicity testnegative
in vitro micronucleus testnegative
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