A-971432
Based on 1 Customer Validation
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 .
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- Purity: 99.31%
- CAS No.: 1240308-45-5
- 화학식: C18H17Cl2NO3
- 분자량:366.24
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보관:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
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Biological Activity
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| CHO | EC50 |
4.1 nM
Compound: 29; A-971432
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Agonist activity at S1P5 receptor (unknown origin) expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation by GTPgammaS binding assay
Agonist activity at S1P5 receptor (unknown origin) expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation by GTPgammaS binding assay
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[PMID: 26509640] |
| CHO | EC50 |
5.7 nM
Compound: 29; A-971432
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Agonist activity at S1P5 receptor (unknown origin) expressed in CHO cell membranes after 30 mins by GTPgammaS binding assay
Agonist activity at S1P5 receptor (unknown origin) expressed in CHO cell membranes after 30 mins by GTPgammaS binding assay
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[PMID: 26509640] |
| CHO | IC50 |
0.362 μM
Compound: 29; A-971432
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Agonist activity at S1P1 receptor (unknown origin) expressed in CHO cell membranes after 30 mins by GTPgammaS binding based MFB method
Agonist activity at S1P1 receptor (unknown origin) expressed in CHO cell membranes after 30 mins by GTPgammaS binding based MFB method
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[PMID: 26509640] |
| HEK293 | IC50 |
>10 μM
Compound: 29; A-971432
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Displacement of [33P]S1P from S1P3 receptor (unknown origin) expressed in HEK cell membranes after 45 to 60 mins by scintillation counting based RLB method
Displacement of [33P]S1P from S1P3 receptor (unknown origin) expressed in HEK cell membranes after 45 to 60 mins by scintillation counting based RLB method
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[PMID: 26509640] |
| HEK293 | IC50 |
0.006 μM
Compound: 29; A-971432
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Displacement of [33P]S1P from S1P5 receptor (unknown origin) expressed in HEK cell membranes after 45 to 60 mins by scintillation counting based RLB method
Displacement of [33P]S1P from S1P5 receptor (unknown origin) expressed in HEK cell membranes after 45 to 60 mins by scintillation counting based RLB method
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[PMID: 26509640] |
| HEK293 | IC50 |
0.362 μM
Compound: 29; A-971432
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Displacement of [33P]S1P from S1P1 receptor (unknown origin) expressed in HEK cell membranes after 45 to 60 mins by scintillation counting based RLB method
Displacement of [33P]S1P from S1P1 receptor (unknown origin) expressed in HEK cell membranes after 45 to 60 mins by scintillation counting based RLB method
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[PMID: 26509640] |
A-971432 (compound 29) (0-10 μM) shows selectivity with IC50s of 0.362, >10, 0.006 μM for S1P1, S1P3, S1P5 respectively[1].
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[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
A-971432 (0.1 mg/kg; P.o.; daily for 21 days) shows pro-cognitive impact in a dose-dependent manner[1].
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[2].
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[2].
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[2].
Pharmacokinetic Parameters of A-971432 in Balb/C mice, SD rat, beagle dog, cyno monkey[1].
| IV | PO | |||||||||||
| species | dose (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 mouse | 2 | plasma | 93 | 7.6 | 8500 | 0.24 | 1.9 | 7.4 | 2.0 | 300 | 4800 | 57 |
| BALB/C mouse | 2 | brain | nd | 9.8 | 3200 (Cmax=133 ng/nL) | nd | nd | 10 | 2-24 | 43 | 1600 | 56 |
| SD rat | 1 | plasm | 93 | 9.0 | 6400 | 0.16 | 1.3 | 14 | 4.3 | 400 | 8700 | >100 |
| SD rat | 2 | brain | 99.5 | nd | nd | nd | nd | 15 | 8 | 120 | 3100 | nd |
| beagle dog | 1 | plasma | 96 | 9.3 | 12000 | 0.09 | 1.2 | 10 | 1.5 | 690 | 11000 | 92 |
| cyno monkey | 1 | plasma | 97 | 3.5 | 6400 | 0.16 | 0.82 | 6.7 | 1.7 | 650 | 5500 | 86 |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Balb/C mice, SD rat, beagle dog, cyno monkey[1]
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Dosage:1, 2 mg/kg
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Administration:P.o. or i.v.
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Result:Showed high oral bioavailability, high exposure, low clearance, a long half-life.
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Animal Model:Male C57BL6J mice[1]
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Dosage:0.1 mg/kg
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Administration:P.o.; daily for 21 days
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Result:Showed pro-cognitive impact in a dose-dependent manner.
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Animal Model:7-week R6/2 mice[2]
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Dosage:0.1 mg/kg
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Administration:I.p.; daily for 4 weeks
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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.
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Animal Model:4-week R6/2 mice[2]
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Dosage:0.1 mg/kg
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Administration:I.p., daily for 2 weeks
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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.
Chemical Information
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CAS No. 1240308-45-5
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Appearance Solid
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분자량 366.24
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화학식 C18H17Cl2NO3
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Color White to off-white
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SMILES
O=C(C1CN(C1)CC2=CC=C(C=C2)OCC3=CC=C(C(Cl)=C3)Cl)O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
DMSO : 2.5 mg/mL (6.83 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
순도&문서
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Data Sheet (278 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1]. 1、Hobson AD,et al. Discovery of A-971432, An Orally Bioavailable Selective Sphingosine-1-Phosphate Receptor 5 (S1P5) Agonist for the Potential Treatment of Neurodegenerative Disorders. J Med Chem. 2015 Dec 10;58(23):9154-70. [Content Brief]
[2]. Di Pardo A, et al. Stimulation of S1PR5 with A-971432, a selective agonist, preserves blood-brain barrier integrity and exerts therapeutic effect in an animal model of Huntington's disease. Hum Mol Genet. 2018 Jul 15;27(14):2490-2501. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.7305 mL | 13.6523 mL | 27.3045 mL | 68.2613 mL |
| 5 mM | 0.5461 mL | 2.7305 mL | 5.4609 mL | 13.6523 mL |
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