| Identification | Back Directory | [Name]
4-(4-tert-butylbenzenesulfonyl)-1-(2,5-dimethoxyphenyl)-5-methyl-1H-1,2,3-triazole | [CAS]
931314-31-7 | [Synonyms]
4-(4-tert-butylbenzenesulfonyl)-1-(2,5-dimethoxyphenyl)-5-methyl-1H-1,2,3-triazole | [Molecular Formula]
C21H25N3O4S | [MDL Number]
MFCD14774311 | [MOL File]
931314-31-7.mol | [Molecular Weight]
415.51 |
| Chemical Properties | Back Directory | [Boiling point ]
612.6±65.0 °C(Predicted) | [density ]
1.22±0.1 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
Chloroform: 10 mg/ml | [form ]
A solid | [pka]
-7.17±0.70(Predicted) | [color ]
Off-white to pink |
| Hazard Information | Back Directory | [Uses]
SPA70 is a potent and selective antagonist of human pregnane X receptor (hPXR), with an IC50 of 540 nM (Ki=390 nM). SPA70 can enhance the chemosensitivity of cancer cells[1]. | [Biological Activity]
SPA70 is a pregnane X receptor (PXR) antagonist (IC50 = 0.51 μM).1 It is selective for PXR over 10 additional nuclear receptors at concentrations greater than 5 μM, as well as over a panel of 384 kinases at 10 μM. SPA70 (0.1-10 μM) inhibits PXR activation induced by rifampicin in HEK293 cells expressing the human receptor. It also inhibits rifampicin-induced activity of the PXR target cytochrome P450 (CYP) isoform 3A4 (CYP3A4) in primary human hepatocytes. SPA70 (200 mg/kg) inhibits PXR agonist-induced CYP3A4-mediated metabolism of midazolam and paclitaxel in human PXR transgenic (hPXR-tg) mice. | [in vivo]
| Animal Model: |
hPXR transgenic mice (male, 8–15 weeks, 20–25 g) + rifampicin-induced Cyp3a11 activation model[1] | | Dosage: | 200 mg/kg (i.p., saline + 7.5% PEG400) | | Administration: | i.p. injection, once daily for 3 days | | Result: | Reduced rifampicin-induced Cyp3a11 mRNA/protein expression by 70% and prolonged anesthesia duration by 2-fold compared to vehicle controls. |
| Animal Model: |
BALB/c Nude mice (male, 6-8 weeks, 20-22 g) + A549/TR xenograft model[2].
| | Dosage: |
30 mg/kg (i.p., 90% PBS + 5% PEG300 + 5% ethanol) | | Administration: | i.p. injection, 3 times/week for 4 weeks | | Result: |
A549/TR xenograft: SPA70 combined with PTX (5 mg/kg) suppressed tumor growth by 89.5% (TGI), decreased P-gp and PXR expression by 60%, and increased cleaved caspase-3-positive cells by 3-fold. |
| Animal Model: | hPXR/CYP3A4 humanized mice (male, 8-10 weeks, 20-25 g) + hemorrhagic shock (HS) model[3] | | Dosage: |
150 mg/kg (i.p., DMSO + cremophor EL) | | Administration: | i.p. injection, once daily for 3 days | | Result: | Blocked rifampicin-induced CYP3A4 expression, reduced hepatic necrosis (Suzuki score: 2.1 vs. 4.5 in vehicle), and attenuated oxidative stress (4-HNE and 8-OHdG staining).
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| [References]
1.Lin, W., Wang, Y.-M., Chai, S.C., et al.SPA70 is a potent antagonist of human pregnane X receptorNat. Commun.8(1)741(2017)
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| Company Name: |
Merck KGaA
|
| Tel: |
21-20338288 |
| Website: |
www.sigmaaldrich.cn |
| Company Name: |
Key Organics Ltd.
|
| Tel: |
+44 (0) 1840-212137 |
| Website: |
www.keyorganics.net |
|