Cyclooxygenase-2 (COX-2) - IC50 = 1.6 μmol/L (inhibition of LPS-stimulated prostaglandin production in human monocytes).[1]
Cyclooxygenase-1 (COX-1) - IC50 = 2.1 μmol/L (inhibition of thromboxane production in human platelets).[1]

(S)-(+)-ibuprofen treatment (HCT-15 and HCA-7 cells; 0-1000 µM; 8 days) decreased concentration-dependent cell survival in both cell lines to a comparable degree [2]. G0/G1 arrest and apoptosis are the outcomes of (S)-(+)-ibuprofen treatment (HCT-15 and HCA-7 cells; 0-1000 µM; 20-72 hours) [2]. (S)-(+)-ibuprofen treatment (HCT-15 and HCA-7 cells; 900 µM; 4-72 hours) resulted in an increase in the cell cycle inhibitory protein p27Kip-1 and a downregulation of cyclins A and B [2]. Platelet aggregation, thromboxane production, and COX activity are all inhibited by (S)-(+)-ibuprofen [1]. (S)-(+)-Ibuprofen, with an IC50 of 61.7 μM, prevents NF-κB from activating upon T cell stimulation [3].

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In vitro, Dexibuprofen (free acid) inhibited COX-2 with an IC50 of 1.6 μmol/L and COX-1 with an IC50 of 2.1 μmol/L. In contrast, the R(-)-enantiomer showed negligible COX-2 inhibition (IC50 >250 μmol/L) and weaker COX-1 inhibition (IC50 34.9 μmol/L). Racemic ibuprofen had an IC50 of 46.7 μmol/L for COX-2 and 6.5 μmol/L for COX-1, suggesting a possible interfering effect of the R(-)-enantiomer on COX-2 inhibition by the S(+) form.[1]
CoA thioesters of both enantiomers also inhibited COX-1 and COX-2 in vitro, but these are formed only from R(-)-ibuprofen in vivo.[1]

In nude mice models, treatment with (15 mg/kg/day; i.p.; five days per week; for four weeks) suppresses the formation of tumors in HCA-7 and HCT-15 xenografts [2].
In a double-blind, parallel-group study of dental pain after molar extraction, Dexibuprofen (free acid) 200 mg provided a more rapid onset of analgesia and better pain relief over the first 3 hours compared to racemic ibuprofen 400 mg. Dexibuprofen (free acid) 400 mg was superior to racemate 400 mg, and both active treatments were superior to placebo.[1]
In a clinical study of patients with osteoarthritis of the hip, Dexibuprofen (free acid) 600 mg/day and 1200 mg/day both significantly improved the WOMAC index from baseline. The 1200 mg/day dose was statistically equivalent to racemic ibuprofen 2400 mg/day. No differences in adverse drug reactions were observed between the two forms.[1]

Neupert et al. (1997) measured COX-1 inhibition by assessing thromboxane B2 production in human platelets after incubation with test compounds. COX-2 inhibition was determined by measuring prostaglandin E2 production in LPS-stimulated human monocytes in aspirin-inactivated whole blood. IC50 values were calculated from concentration-response curves. For Dexibuprofen (free acid), the IC50 for COX-2 was 1.6 μmol/L and for COX-1 was 2.1 μmol/L. The CoA thioesters of both enantiomers were also tested and found to inhibit both COX isoforms, but these intermediates are not formed after administration of the S(+) enantiomer.[1]
Boneberg et al. (1996) used human purified COX-1 and COX-2 enzymes and also reported inhibitory effects, but their results did not support competition between enantiomers for the enzyme active site.[1]

Cell Proliferation Assay[2]
Cell Types: HCT-15 and HCA-7 Cell
Tested Concentrations: 0 µM, 200 µM, 400 µM, 600 µM, 700 µM, 800 µM, 900 µM and 1000 µM
Incubation Duration: 8 days
Experimental Results: Two The concentration-dependent decrease in cell viability was similar among the cell lines.

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Cell cycle analysis[2]
Cell Types: HCT-15 and HCA-7 Cell
Tested Concentrations: 0 µM, 200 µM, 400 µM, 600 µM, 800 µM, 900 µM and 1000 µM
Incubation Duration: 24 hrs (hours) (HCT-15) or 20 hrs (hours) (HCA-7)
Experimental Results: Causes G0/G1 phase obstruction.

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Apoptosis analysis[2]
Cell Types: HCT-15 and HCA-7 Cell
Tested Concentrations: 0 µM, 200 µM, 400 µM, 600 µM, 800 µM, 900 µM and 1000 µM
Incubation Duration: 72 hrs (hours)
Experimental Results: Induction of apoptosis Death.

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Western Blot Analysis[2]
Cell Types: HCT-15 and HCA-7 Cell
Tested Concentrations: 900 µM
Incubation Duration: 4 hrs (hours), 8 hrs (hours), 16 hrs (hours), 24 hrs (hours), 32 hrs (hours), 48 hrs (hours) and 72 hrs (hours)
Experimental Results: Cyclin levels diminished D1 protein.

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The cell-based assays used to determine COX inhibition included: human platelets (for COX-1) stimulated with arachidonic acid to produce thromboxane B2; and human monocytes in whole blood stimulated with lipopolysaccharide (LPS) to induce COX-2 and produce prostaglandin E2. Dexibuprofen (free acid) was added at various concentrations, and after incubation, the production of thromboxane B2 or prostaglandin E2 was measured by immunoassay to calculate IC50 values.[1]

Animal/Disease Models: NMRI (nu/nu) male mice (6-8 weeks old) injected with HCA-7 and HCT-15 cells [2]
Doses: 15 mg/kg/day
Route of Administration: intraperitoneal (ip) injection; five days per week; continuous 4-week
Experimental Results: Inhibition of tumor growth in mouse HCA-7 and HCT-15 xenografts.

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In nude mice, Dexibuprofen (free acid) was suspended in PBS (pH 7) and administered intraperitoneally at 15 mg/kg/day, five days a week for three to four weeks. Treatment started 3 days after subcutaneous injection of tumor cells (HCT-15: 1×10⁷ cells/mouse; HCA-7: 3×10⁷ cells/mouse). Tumor volume was measured three times per week with a caliper. After the last dose, blood samples were collected at 5, 15, 30, 45, 60, 120 min, plasma separated, and S- and R-ibuprofen concentrations determined by stereoselective HPLC after solid phase extraction.[2]

Absorption, Distribution and Excretion
Following oral administration of a tablet containing 300 mg dextroibuprofen, the time to peak plasma concentration is 2.25–5 hours. For more information, see [Ibuprofen]. It is primarily excreted via the kidneys. For more information, see [Ibuprofen]. For more information, see [Ibuprofen]. For more information, see [Ibuprofen]. For more information, see [Ibuprofen]. Metabolisms/Metabolites For more information, see [Ibuprofen]. Known metabolites of (S)-(+)-ibuprofen include 2-hydroxyibuprofen and 3-hydroxyibuprofen. Biological Half-Life The half-life of an oral 300 mg dextroibuprofen tablet is 2.2–4.7 hours. For more information, see [Ibuprofen].

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Dexibuprofen (free acid) is rapidly absorbed after oral administration, with an absorption half-life of about 30 minutes for conventional dosage forms. Bioavailability is approximately 100%. It has a small volume of distribution (10–12 L) due to extensive plasma protein binding (fraction unbound = 0.008). Clearance is mainly hepatic (50–150 mL/min), with low hepatic extraction ratio. The drug is almost exclusively eliminated by metabolism (glucuronidation and oxidation), with greater than 90% of an oral dose recovered as metabolites in urine. The half-life is short, requiring 3–4 doses per day in chronic conditions. Unlike R(-)-ibuprofen, Dexibuprofen (free acid) does not undergo chiral inversion nor is it incorporated into triglycerides, and it does not form CoA thioesters.[1]

Protein Binding
For more information, please refer to [ibuprofen].

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No specific toxicity parameters (e.g., LD50) are reported. The adverse event profile of Dexibuprofen (free acid) is similar to that of racemic ibuprofen. Potential toxicity concerns include the formation of acyl glucuronide metabolites that can bind to endogenous proteins, possibly leading to hypersensitivity reactions. However, the relative propensity of the S(+) enantiomer to form such adducts compared to the racemate is unknown.[1]

[1]. Comparative pharmacology of S(+)-ibuprofen and (RS)-ibuprofen. Clin Rheumatol. 2001 Nov;20 Suppl 1:S9-14.

[2]. Evidence of COX-2 independent induction of apoptosis and cell cycle block in human colon carcinoma cells after S- or R-ibuprofen treatment. Eur J Pharmacol. 2006 Jul 1;540(1-3):24-33.

[3]. Modulation of transcription factor NF-kappaB by enantiomers of the nonsteroidal drug ibuprofen. Br J Pharmacol. 1998 Feb;123(4):645-52.

Dextrorotatory ibuprofen is a type of ibuprofen. It is a non-narcotic analgesic and a nonsteroidal anti-inflammatory drug (NSAID). It is the enantiomer of levorotatory ibuprofen. Dextrorotatory ibuprofen, or S(+)-ibuprofen, is a nonsteroidal anti-inflammatory drug (NSAID). It is the pharmacologically active enantiomer of racemic ibuprofen, and its physicochemical properties differ from those of racemic ibuprofen. Due to the higher concentration of the active S enantiomer, dextrorotatory ibuprofen is considered to have higher pharmacological activity, better tolerability, and better safety than ibuprofen. Compared to racemic ibuprofen, dextrorotatory ibuprofen dissolves more slowly in simulated gastric and intestinal fluids and has higher oral bioavailability. For information on metabolism, enzymes, carriers, and transport proteins, please refer to [Ibuprofen]. See also: Ibuprofen (note moved to).

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Drug Indications
For more information, please refer to [Ibuprofen].

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Mechanism of Action
Similar to common nonsteroidal anti-inflammatory drugs (NSAIDs), dextro-ibuprofen is the active enantiomer of ibuprofen. It inhibits prostaglandin synthesis in inflammatory cells by inhibiting the COX-2 isoenzyme of arachidonic acid cyclooxygenase (COX). For more information, please refer to [ibuprofen].

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Pharmacodynamics
For more information, please refer to [ibuprofen].

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Dexibuprofen (free acid) is the active COX-inhibiting enantiomer of ibuprofen. Its pharmacological advantages over racemic ibuprofen include: reduced metabolic load (no chiral inversion or lipid metabolism involvement), avoidance of pharmacokinetic variability from inversion, and the potential for lower doses (e.g., 200 mg S(+) vs 400 mg racemate in acute pain, 1200 mg/day vs 2400 mg/day in osteoarthritis). The theoretical dose ratio for equivalent S(+) exposure is 0.75, but clinical studies suggest a ratio of 0.5 may suffice, possibly because the R(-)-enantiomer in the racemate interferes with S(+)-ibuprofen's action on COX-2 without affecting COX-1. This interference is supported by in vitro data showing that racemic ibuprofen has a much higher (10-fold) IC50 for COX-2 than expected, while COX-1 IC50 values are as predicted.[1]

206.13

51146-56-6

Ibuprofen;15687-27-1;(S)-(+)-Ibuprofen-d3;1329643-44-8;(R)-(-)-Ibuprofen;51146-57-7;Ibuprofen sodium;31121-93-4;Ibuprofen-d3;121662-14-4

39912

White to off-white solid powder

1.0±0.1 g/cm3

319.6±11.0 °C at 760 mmHg

49-53ºC

216.7±14.4 °C

0.0±0.7 mmHg at 25°C

1.519

3.72

1

2

4

15

203

1

OC([C@H](C1=CC=C(CC(C)C)C=C1)C)=O

HEFNNWSXXWATRW-JTQLQIEISA-N

InChI=1S/C13H18O2/c1-9(2)8-11-4-6-12(7-5-11)10(3)13(14)15/h4-7,9-10H,8H2,1-3H3,(H,14,15)/t10-/m0/s1

(2S)-2-[4-(2-methylpropyl)phenyl]propanoic acid

L-669,455, MK 233 Dexibuprofen (free acid) MK-233Dexibuprofen Doctrin L 669455

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~484.78 mM)
Ethanol : ~100 mg/mL (~484.78 mM)
H2O : ~1 mg/mL (~4.85 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.12 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (12.12 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (12.12 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: ≥ 2.5 mg/mL (12.12 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix well.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 5: 10% EtOH + 90% Corn Oil

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Solubility in Formulation 6: 6.67 mg/mL (32.33 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)