| Identification | Back Directory | [Name]
AS2717638 | [CAS]
2148339-28-8 | [Synonyms]
AS2717638
1(2H)-Isoquinolinone, 6,7-dimethoxy-2-(5-methyl-1,2-benzisoxazol-3-yl)-4-(1-piperidinylcarbonyl)- | [Molecular Formula]
C25H25N3O5 | [MDL Number]
MFCD31813748 | [MOL File]
2148339-28-8.mol | [Molecular Weight]
447.48 |
| Chemical Properties | Back Directory | [Boiling point ]
712.5±60.0 °C(Predicted) | [density ]
1.321±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMF: 2 mg/ml; DMSO: 2 mg/ml | [form ]
A solid | [pka]
-1.17±0.20(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
AS2717638 is a highly selective, brain-penetrant and orally active lysophosphatidic acid receptor 5 (LPA5) antagonist with an IC50 value of 38 nM. AS2717638 is highly selective and shows no significant antagonistic activity against other LPA receptors (LPA1, LPA2, and LPA3). AS2717638 can be used in the research of pain and neuroinflammation-related diseases[1][2]. | [Biological Activity]
Orally activepotent and selective lysophosphatidic acid (LPA) receptor LPAR5 (LPA5) antagonist with analgesic efficacy in vivo.
AS2717638 is an orally activepotent and selective lysophosphatidic acid (LPA) receptor LPAR5 (LPA5) antagonist (h/m/r LPA5 Ki = 9.1/7.3/16 nM) th at blocks LPA-induced activation of human LPA5-expressing cells (cAMP accumulation IC50 = 38 nM)but not LPA1LPA2 or LPA3 transfectants (Ca2+ mobilization IC50 >10 μM) and displays much reduced or little affinity toward 20 other receptors and channels. AS2717638 exhibits analgesic efficacy in mice (10 & 30 mg/kg p.o. against allodynia caused by 10 ng PGE2300 ng PGF2αor 3 ng AMPA per mouse via i.t.) and rats (10 mg/kg p.o. against mechanical allodyniathermal hyperalgesia and adjuvant-induced inflammatory pain) in vivo. | [in vivo]
AS2717638 (3-30 mg/kg; oral administration; 1 h before the experiment; single dose) inhibits allodynia in mouse models of allodynia induced by LPA or GGPP[1].
AS2717638 (10-30 mg/kg; oral administration; 1 h before the experiment; single dose) alleviates allodynia in mouse models of allodynia induced by PGE2, PGF2α, or AMPA[1].
AS2717638 (10 mg/kg; oral administration; 2 h before the experiment; single dose) ameliorates static mechanical allodynia and thermal hyperalgesia in a rat model of neuropathic pain induced by chronic constriction injury (CCI)[1].
AS2717638 (10 mg/kg; oral administration; 2 h before the experiment; single dose) improves hind paw weight - bearing ability in a rat model of inflammatory pain induced by adjuvant[1].
AS2717638 (10 mg/kg; oral administration; before the experiment; single dose) reduces LPS (HY-D1056)-induced iNOS, TNFα, IL-6, and CXCL2 mRNA expression, improves the expression of neuroinflammation - related proteins, and reduces peripheral cytokine concentrations in a mouse endotoxemia model[2].
| Animal Model: | Male ICR mice, LPA- and GGPP-induced allodynia model[1] | | Dosage: | 1 mg/kg, 3 mg/kg, 10 mg/kg, 30 mg/kg (dissolved in 30% propylene glycol solvent in distilled water) | | Administration: | Orally, administered once, 1 h before i.t. injection of LPA or GGPP | | Result: | Significantly inhibited LPA- and GGPP-induced allodynia. |
| Animal Model: | Male ICR mice, PGE2-, PGF2α- or AMPA-induced allodynia model[1] | | Dosage: | 3 mg/kg, 10 mg/kg, 30 mg/kg (dissolved in 30% propylene glycol solvent in distilled water) | | Administration: | Orally, administered once, 1 h before i.t. injection of PGE2, PGF2α, or AMPA | | Result: | Significantly alleviated allodynia in all three pain sensitizer-induced pain models. |
| Animal Model: | Male Sprague-Dawley rats, chronic constriction injury (CCI)-induced neuropathic pain model[1] | | Dosage: | 10 mg/kg (dissolved in 30% propylene glycol solvent in distilled water) | | Administration: | Orally, administered once, 2 h before the von Frey and plantar tests | | Result: | Significantly ameliorated both static mechanical allodynia and thermal hyperalgesia in CCI rats. |
| Animal Model: | Female Lewis rats, adjuvant-induced inflammatory pain model[1] | | Dosage: | 10 mg/kg (dissolved in 30% propylene glycol solvent in distilled water) | | Administration: | 10 mg/kg (dissolved in 30% propylene glycol solvent in distilled water) | | Result: | Significantly improved weight bearing difference in a rat model of adjuvant-induced inflammatory pain. |
| Animal Model: | C57BL/6J mice (8-10 weeks, 20-30 g), mouse endotoxemia model[2] | | Dosage: | 10 mg/kg | | Administration: | Orally, administered once, 24 h before sacrifice | | Result: | Significantly reduced the mRNA expression of iNOS, TNFα, IL6, and CXCL2.
Also amended the expression of neuroinflammatory parameters such as TLR4, Iba1, GFAP, COX-2, and the Bax/Bcl2 ratio. |
| [IC 50]
LPA5 Receptor: 38 nM (IC50, Human); LPA5 Receptor: 9.1 nM (Ki, Human); LPA5 Receptor: 16 nM (Ki, Rat); LPA5 Receptor: 7.3 nM (Ki, Mouse) | [storage]
Store at -20°C | [References]
[1] Murai N, et al. Analgesic effects of novel lysophosphatidic acid receptor 5 antagonist AS2717638 in rodents. Neuropharmacology. 2017 Nov;126:97-107. DOI:10.1016/j.neuropharm.2017.08.032
[2] Joshi L, et al. Inhibition of Autotaxin and Lysophosphatidic Acid Receptor 5 Attenuates Neuroinflammation in LPS-Activated BV-2 Microglia and a Mouse Endotoxemia Model. Int J Mol Sci. 2021 Aug 7;22(16):8519. DOI:10.3390/ijms22168519 |
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| Company Name: |
BOC Sciences
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1-631-485-4226; 16314854226 |
| Website: |
https://www.bocsci.com |
| Company Name: |
Merck KGaA
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21-20338288 |
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www.sigmaaldrich.cn |
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