产品
编 号：F087074
分子式：C18H17Cl2NO3
分子量：366.24
分子式：C18H17Cl2NO3
分子量：366.24
产品类型
规格
价格
是否有货
5mg
询价
询价
结构图
CAS No: 1240308-45-5
产品详情
生物活性：
A-971432 is a potent, selective and orally active sphingosine-1-phosphate (S1P) receptor 5 agonist with IC50s of .362, >10, 0.006 μM for S1P1, S1P3, S1P5 respectively. A-971432 protects blood–brain barrier (BBB) homeostasis. A-971432 reverses age-related cognitive decline. A-971432 has the potential for the research of alzheimer’s disease or multiple sclerosis .
体内研究：
A-971432 (1, 2 mg/kg; p.o.) shows excellent PK characteristics and oral bioavailability.A-971432 (0.1 mg/kg; P.o.; daily for 21 days) shows pro-cognitive impact in a dose-dependent manner.A-971432 (11 weeks R6/2 mice; 0.1 mg/kg; i.p.) increases the phosphorylation of AKT and ERK and significantly incremented the levels of BDNF in the cortex.A-971432 (0.1 mg/kg; i.p.) attenuates the classic progressive BBB leakage and therefore the FITC-albumin extravasation in striatal parenchyma, and protects blood–brain barrier (BBB) homeostasis and suppresses aggregation of mHtt in the CNS blood vessels.A-971432 (0.1 mg/kg; i.p.; daily for 4 weeks) prevents the worsening of motor deficit in symptomatic R6/2 mice by chronic infusion.Pharmacokinetic Parameters of A-971432 in Balb/C mice, SD rat, beagle dog, cyno monkey.IVPO
speciesdose (mg/kg)sample analyzed)protein binding (%)t1/2 (h)AUC (ng.h/mL)VL (L/h/kg)Vss(L/kg)t1/2 (h)tmax (h)Cmax (ng/mL)AUC (ng.h/mL)F(%)
BALB/C mouse2plasma937.685000.241.97.42.0300480057
BALB/C mouse2brainnd9.83200 (Cmax=133 ng/nL)ndnd102-2443160056
SD rat1plasm939.064000.161.3144.34008700>100
SD rat2brain99.5ndndndnd1581203100nd
beagle dog1plasma969.3120000.091.2101.56901100092
cyno monkey1plasma973.564000.160.826.71.7650550086
Balb/C mice, SD rat, beagle dog, cyno monkey; p.o. or i.v.; 2 mg/kg for Balb/C mice, SD rat; 1mg/kg forSD rat, beagle dog, cyno monkey.Animal Model:Balb/C mice, SD rat, beagle dog, cyno monkey
Dosage:1, 2 mg/kg
Administration:P.o. or i.v.
Result:Showed high oral bioavailability, high exposure, low clearance, a long half-life.
Animal Model:Male C57BL6J mice
Dosage:0.1 mg/kg
Administration:P.o.; daily for 21 days
Result:Showed pro-cognitive impact in a dose-dependent manner.
Animal Model:7-week R6/2 mice
Dosage:0.1 mg/kg
Administration:I.p.; daily for 4 weeks
Result:Restored normal motor function within the first week of treatment, and preserved them from the gradual motor deficit, classically occurring during the disease, for the entire period of the treatment.
Animal Model:4-week R6/2 mice
Dosage:0.1 mg/kg
Administration:I.p., daily for 2 weeks
Result:Preserved BBB integrity and delayed the onset of motor symptoms in R6/2 mice and suppressed aggregation of mHtt in the CNS blood vessels.
体外研究：
A-971432 (compound 29) (0-10 μM) shows selectivity with IC50s of 0.362, >10, 0.006 μM for S1P1, S1P3, S1P5 respectively.A-971432 (0.1-1000 nM) induces full agonism with an EC50s of 5.7 nM and 4.1 nM for HEK cells and CHO cells, respectively.
A-971432 is a potent, selective and orally active sphingosine-1-phosphate (S1P) receptor 5 agonist with IC50s of .362, >10, 0.006 μM for S1P1, S1P3, S1P5 respectively. A-971432 protects blood–brain barrier (BBB) homeostasis. A-971432 reverses age-related cognitive decline. A-971432 has the potential for the research of alzheimer’s disease or multiple sclerosis .
体内研究：
A-971432 (1, 2 mg/kg; p.o.) shows excellent PK characteristics and oral bioavailability.A-971432 (0.1 mg/kg; P.o.; daily for 21 days) shows pro-cognitive impact in a dose-dependent manner.A-971432 (11 weeks R6/2 mice; 0.1 mg/kg; i.p.) increases the phosphorylation of AKT and ERK and significantly incremented the levels of BDNF in the cortex.A-971432 (0.1 mg/kg; i.p.) attenuates the classic progressive BBB leakage and therefore the FITC-albumin extravasation in striatal parenchyma, and protects blood–brain barrier (BBB) homeostasis and suppresses aggregation of mHtt in the CNS blood vessels.A-971432 (0.1 mg/kg; i.p.; daily for 4 weeks) prevents the worsening of motor deficit in symptomatic R6/2 mice by chronic infusion.Pharmacokinetic Parameters of A-971432 in Balb/C mice, SD rat, beagle dog, cyno monkey.IVPO
speciesdose (mg/kg)sample analyzed)protein binding (%)t1/2 (h)AUC (ng.h/mL)VL (L/h/kg)Vss(L/kg)t1/2 (h)tmax (h)Cmax (ng/mL)AUC (ng.h/mL)F(%)
BALB/C mouse2plasma937.685000.241.97.42.0300480057
BALB/C mouse2brainnd9.83200 (Cmax=133 ng/nL)ndnd102-2443160056
SD rat1plasm939.064000.161.3144.34008700>100
SD rat2brain99.5ndndndnd1581203100nd
beagle dog1plasma969.3120000.091.2101.56901100092
cyno monkey1plasma973.564000.160.826.71.7650550086
Balb/C mice, SD rat, beagle dog, cyno monkey; p.o. or i.v.; 2 mg/kg for Balb/C mice, SD rat; 1mg/kg forSD rat, beagle dog, cyno monkey.Animal Model:Balb/C mice, SD rat, beagle dog, cyno monkey
Dosage:1, 2 mg/kg
Administration:P.o. or i.v.
Result:Showed high oral bioavailability, high exposure, low clearance, a long half-life.
Animal Model:Male C57BL6J mice
Dosage:0.1 mg/kg
Administration:P.o.; daily for 21 days
Result:Showed pro-cognitive impact in a dose-dependent manner.
Animal Model:7-week R6/2 mice
Dosage:0.1 mg/kg
Administration:I.p.; daily for 4 weeks
Result:Restored normal motor function within the first week of treatment, and preserved them from the gradual motor deficit, classically occurring during the disease, for the entire period of the treatment.
Animal Model:4-week R6/2 mice
Dosage:0.1 mg/kg
Administration:I.p., daily for 2 weeks
Result:Preserved BBB integrity and delayed the onset of motor symptoms in R6/2 mice and suppressed aggregation of mHtt in the CNS blood vessels.
体外研究：
A-971432 (compound 29) (0-10 μM) shows selectivity with IC50s of 0.362, >10, 0.006 μM for S1P1, S1P3, S1P5 respectively.A-971432 (0.1-1000 nM) induces full agonism with an EC50s of 5.7 nM and 4.1 nM for HEK cells and CHO cells, respectively.
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