sodium (2S)-2-(6-methoxynaphthalen-2-yl)propanoate

• ChemBase ID: 72768
• Molecular Formular: C14H13NaO3
• Molecular Mass: 252.24099
• Monoisotopic Mass: 252.07623856
• SMILES: c1c(cc2c(c1)cc(cc2)[C@@H](C(=O)O[Na])C)OC
• Canonical SMILES: [Na]OC(=O)[C@H](c1ccc2c(c1)ccc(c2)OC)C
• InChI: InChI=1S/C14H14O3.Na/c1-9(14(15)16)10-3-4-12-8-13(17-2)6-5-11(12)7-10;/h3-9H,1-2H3,(H,15,16);/q;+1/p-1/t9-;/m0./s1
• InChIKey: CDBRNDSHEYLDJV-FVGYRXGTSA-M

NAMES AND DATABASE IDS

Names

• IUPAC name: sodium (2S)-2-(6-methoxynaphthalen-2-yl)propanoate
• IUPAC Traditional name: naproxen sodium
• Synonyms: Anaprox; Miranax; Naprelan; Naposin; Naproxen sodium

Database IDs

• CAS Number: 26159-34-2
• PubChem SID: 162037689
• PubChem CID: 23681059

CALCULATED PROPERTIES

• H Acceptors: 2
• H Donor: 0
• LogD (pH = 5.5): 3.3006
• LogD (pH = 7.4): 3.3006
• Log P: 3.3006
• Molar Refractivity: 63.9259 cm^3
• Polarizability: 28.281672 Å^3
• Polar Surface Area: 35.53 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

PROPERTIES

Safety Information

• Storage Condition: -20°C

Product Information

• Salt Data: Sodium

DETAILS

Selleck Chemicals - S1626

Research Area

• Description: Neurological Disease

Biological Activity

• Description: Naproxen (Aleve, Anaprox) is a COX inhibitor for COX-1 and COX-2 with IC50 of 2.2 μg/mL and 1.3 μg/mL, respectively.
• Targets: COX-1; COX-2
• IC50: 2.2 μg/mL; 1.3 μg/mL ^[1]
• In Vitro: Naproxen is approximately equipotent inhibitor of COX-1 and COX-2 in intact cells with IC50 of 2.2 μg/mL and 1.3 μg/mL, respectively. ^[1] Naproxen decreases the in vitro LPS-induced PGE₂ and TXB₂ production in rats and humans with IC50 of 30.7 μM and 79.5 μM for PGE₂ inhibition, 72.4 μM and 48.3 μM for TXB₂ inhibition, respectively. ^[2] Naproxen produces concentration-related inhibition of TXB₂ production from human platelets and LPS-induced TXB₂ production from human mononuclear cells with plC50 values (-log concentration inhibiting TXB₂ by 50%) of 5.7 and 6.4, respectively, and exhibits slightly inhibitory selectivity for constitutive and induced COX-2 with IC50 COX-1/IC50 COX-2 of 6.3. ^[3] Only high concentration of Naproxen can significantly induce apoptosis at 48 hours in HCA-7 colon cancer cells with IC50 of 1.45 mM. ^[4]
• In Vivo: Administration of Naproxen reduces the LPS-induced PGE₂ and TXB₂ production in vivo in rats with IC50 values of 12.8 μM and 5.9 μM, respectively, which represents that Naproxen is a nonselective COX inhibitor with the log IC50 ratio (COX-2/COX-1) of 0.34. ^[2] Naproxen displays IC50 of 27 μM for analgesia in a rat model with carrageenan-induced arthritis and IC50 of 40 μM for antipyretics in a yeast-induced fever rat model, while exhibits inhibition of PGE₂ with IC50 of 13 μM and TXB₂ with IC50 of 5 μM. ^[5]
• Clinical Trials: Phase IV completed in testing the effect on blood pressure of sumatriptan and Naproxen sodium combination tablets, tablets containing only sumatriptan, and tablets containing only Naproxen sodium when these drugs are taken to treat migraine headaches that occur during a 6-month period.
• Features: Naproxen displays approximately equipotent inhibitory selectivity for COX-1 and COX-2 in intact cells.

Protocol

• Protocol: Kinase Assay ^[1]
• COX-1 and COX-2 activities in intact cells: For the determination of COX-1 and COX-2 inhibition, bovine aortic endothelial cells (BAEC) are incubated for 30 minutes with Naproxen (0.1 ng/mL to 1 mg/mL), and cultured J774.2 macrophages are treated with endotoxin at 1 μg/mL for 12 hours to induce COX-2 followed by incubated for 30 minutes with Naproxen (0.1 ng/mL to 1 mg/mL), respectively. Arachidonic acid (30 μM) is then added, and the cells are incubated for a further 15 minutes at 37 °C. The medium is then removed, and radioimmunoassay is used to measure the formation of 6-keto-PGF1α, PGE₂, thromboxane B₂, or PGF_2α for the assessment of IC50 for COX-1 and COX-2.
• Protocol: Cell Assay ^[4]
• Cell Lines: Human colon cancer HCA-7 cell lines
• Concentrations: Dissolved in culture medium, final concentration ~20 mM
• Incubation Time: 24 and 48 hours
• Methods: Cells are exposed to Naproxen for 24 and 48 hours, respectively. At the end of incubation, cells are harvested by trypsinization, stained with trypan blue solution (0.04% wt/vol) and counted in a Neubauer haemocytometer chamber for the determination of cell viability.
• Protocol: Animal Study ^[2]
• Animal Models: Male Sprague-Dawley rats
• Formulation: Dissolved in 0.9% NaCl
• Doses: 2.5, 10 or 25 mg/kg
• Administration: Intravenously (i.v.) infusion or intraperitoneal (i.p.) injection

References

• References: [1] Mitchell JA, et al. Proc Natl Acad Sci, 1993, 90(24), 11693-11697.
• References: [2] Huntjens DR, et al. Br J Pharmacol, 2006, 148(4), 396-404.
• References: [3] Grossman CJ, et al. Inflamm Res, 1995, 44(6), 253-257.
• References: [4] Tavolari S, et al. Carcinogenesis, 2008, 29(2), 371-380.
• References: [5] Krekels EH, et al. Pharm Res, 2011, 28(7), 1561-1576.

REFERENCES

• Mitchell JA, et al. Proc Natl Acad Sci, 1993, 90(24), 11693-11697.
• Huntjens DR, et al. Br J Pharmacol, 2006, 148(4), 396-404.
• Grossman CJ, et al. Inflamm Res, 1995, 44(6), 253-257.
• Tavolari S, et al. Carcinogenesis, 2008, 29(2), 371-380.
• Krekels EH, et al. Pharm Res, 2011, 28(7), 1561-1576.