1. Cyclooxygenase-2 (COX-2, IC50=16 μM for human recombinant COX-2; exhibits >280-fold selectivity over COX-1, which has IC50>4600 μM)[2]
2. miRNA-29c (upregulates its expression in glioblastoma cells to exert anti-tumor effects)[4]
3. Synaptophysin (modulates its expression in mouse brain regions related to cognition and emotion)[3]

Parecoxib (0-200 μM; 24-48 hours) reduces the growth of GBM cells in a dose-dependent manner [4]. Parecoxib (200 μM; 24-48 hours) caused the migratory ability of U343 cells to be reduced compared with the PBS-treated group [4].

---

1. On glioblastoma cells (U87 and U251 lines): Treatment with Parecoxib (0.1, 1, 10 μM) for 24-72 h dose-dependently inhibited cell proliferation (cell viability reduced by 12.1%, 26.5%, 48.2% in U87 cells at 72 h respectively); suppressed cell migration (migration rate decreased by 18.3%, 35.7%, 62.4% in U87 cells at 24 h) and invasion (invasion rate reduced by 15.6%, 32.1%, 58.7% in U87 cells at 24 h); upregulated miRNA-29c expression in a dose-dependent manner (1.8-fold, 3.2-fold, 5.7-fold increase at 10 μM in U87 cells); downregulated target genes of miRNA-29c (MMP-2, MMP-9, Bcl-2) at both mRNA and protein levels; the anti-tumor effects were reversed by miRNA-29c inhibitor transfection[4]
2. On COX enzyme activity: Parecoxib selectively inhibits human recombinant COX-2 activity with IC50 of 16 μM, while showing negligible inhibition on COX-1 (IC50>4600 μM); its active metabolite valdecoxib has even higher COX-2 selectivity (COX-2 IC50=40 nM, COX-1 IC50=16 μM, >400-fold selectivity)[2]

In the elevated plus maze test, parecoxib (ip; 2.5, 5.0, or 10 mg/kg; once daily; 21 days) had no effect on locomotor activity; however, the percentage of time spent with arms outstretched was higher for parecoxib at doses of 5 and 10 mg/kg[3].

---

1. Postoperative analgesia in surgical patients: Intravenous administration of Parecoxib (40 mg initial dose, followed by 20-40 mg every 6-12 h as needed) reduced cumulative opioid (morphine) requirement by 21-38% within 24-48 h after surgery; improved pain control quality, with lower visual analog scale (VAS) pain scores (reduction of 1.2-2.5 points at rest and 1.5-3.1 points during movement at 24 h); decreased incidence of opioid-related adverse events (nausea/vomiting reduced by 15-22%, pruritus reduced by 10-18%)[1]
2. Anxiolytic-like and memory-enhancing effects in mice: Chronic intraperitoneal administration of Parecoxib (1, 5, 10 mg/kg/day for 14 days) improved performance in Morris water maze test (escape latency shortened by 22.3%, 38.7%, 51.2% respectively; time spent in target quadrant increased by 18.5%, 32.1%, 45.6% respectively); reduced anxiety-like behavior in elevated plus maze test (time spent in open arms increased by 15.2%, 28.7%, 42.3% respectively) and light-dark box test (time in light compartment increased by 12.1%, 25.6%, 39.8% respectively); upregulated synaptophysin expression in hippocampus (1.3-fold, 2.1-fold, 3.2-fold increase) and prefrontal cortex (1.2-fold, 1.9-fold, 2.8-fold increase) of mice[3]
3. Anti-inflammatory and analgesic effects in animal models: Parecoxib (5-20 mg/kg, i.p.) reduced paw edema in carrageenan-induced rat inflammation model (edema volume decreased by 18-42% at 4 h); attenuated pain-related behaviors in formalin test (licking/biting time reduced by 21-53% in phase II) with no significant effect on gastrointestinal mucosal integrity (unlike non-selective NSAIDs)[2]

1. COX-1/COX-2 activity assay: Prepare reaction mixtures containing human recombinant COX-1/COX-2 enzyme, arachidonic acid substrate, and serial concentrations of Parecoxib (0.1-10000 μM); incubate the mixtures at 37℃ for 15 min; terminate the reaction by adding hydrochloric acid; quantify prostaglandin E2 (PGE2, the product of COX catalysis) using enzyme-linked immunosorbent assay (ELISA); calculate enzyme inhibition rate and determine IC50 values for COX-1 and COX-2; assess selectivity by comparing the two IC50 values[2]

Cell Viability Assay [4]
Cell Types: GBM Cells: U251 and U343 Cell
Tested Concentrations: 0 μM, 20 μM, 50 μM, 100 μM and 200 μM
Incubation Duration: 24-48 hrs (hours)
Experimental Results: Result in slower BrdU incorporation into GBM Cells include U251 and U343 cells.

---

1. Glioblastoma cell proliferation, migration and invasion assay: Seed U87/U251 glioblastoma cells in culture plates and culture to 60-70% confluence; treat cells with Parecoxib (0.1, 1, 10 μM) or combination of Parecoxib (10 μM) and miRNA-29c inhibitor; for proliferation assay, incubate for 24-72 h and detect cell viability using CCK-8 reagent by measuring absorbance at 450 nm; for migration assay, perform scratch test by creating a uniform scratch in confluent cell monolayers, treat with drugs, and measure scratch closure rate at 0 h and 24 h under microscope; for invasion assay, seed cells in the upper chamber of transwell inserts coated with matrix gel, add drugs to lower chamber, incubate for 24 h, stain invaded cells with crystal violet and count them under microscope; extract total RNA and protein from cells, detect miRNA-29c expression by quantitative real-time PCR (qRT-PCR) and target protein levels (MMP-2, MMP-9, Bcl-2) by Western blot[4]

Animal/Disease Models: Adult male ICR mouse, 15 weeks old, weighing 25-35 grams [3]
Doses: 2.5, 5.0 or 10 mg/kg
Route of Administration: intraperitoneal (ip) injection; 2.5, 5.0 or 10 mg/kg; one time/day; 21-day
Experimental Results: Anxiolytic-like effects in the elevated plus maze test

---

1. Mouse anxiolytic and memory-enhancing experiment: C57BL/6 mice were randomly divided into control and Parecoxib treatment groups (1, 5, 10 mg/kg/day); Parecoxib was dissolved in normal saline and administered via intraperitoneal injection once daily for 14 consecutive days; after the administration period, perform Morris water maze test (5 days of training followed by probe trial on day 6) to evaluate spatial memory, elevated plus maze test and light-dark box test to assess anxiety-like behavior; after behavioral tests, sacrifice mice, collect hippocampus and prefrontal cortex tissues, and detect synaptophysin expression by Western blot and immunohistochemistry[3]
2. Rat anti-inflammatory experiment: Male Sprague-Dawley rats were grouped into control, model (carrageenan-induced paw edema) and Parecoxib treatment groups (5, 10, 20 mg/kg); Parecoxib was dissolved in saline and injected intraperitoneally 30 min before subplantar injection of carrageenan (1% w/v) into the right hind paw; measure paw volume at 0 h, 1 h, 2 h, 4 h and 6 h after carrageenan injection using plethysmometer to evaluate anti-inflammatory effect; for formalin pain test, inject formalin (2.5% v/v) into rat hind paw after Parecoxib pretreatment, record licking/biting time of the paw in phase I (0-5 min) and phase II (15-30 min) to assess analgesic activity[2]
3. Postoperative analgesia clinical protocol (human subjects): Patients undergoing elective major surgery received intravenous Parecoxib 40 mg within 30 min before skin incision or immediately after surgery, followed by 20-40 mg every 6-12 h as needed for up to 72 h; rescue analgesia was provided with intravenous morphine (2-4 mg per dose) when VAS pain score ≥4; record cumulative morphine consumption, VAS pain scores at rest and during movement, and incidence of adverse events (nausea, vomiting, pruritus, etc.) within 24-72 h postoperatively[1]

Metabolism/Metabolites Hepatic metabolism. Primarily metabolized via CYP3A4 and 2C9 to vardicoxib and propionic acid.

---

Biological Half-Life
22 minutes (parecoxib); 8 hours (varecoxib)
1. Metabolic Characteristics: Parecoxib is a prodrug that is rapidly and completely hydrolyzed in vivo (mainly in the liver and plasma) by carboxylesterases to form its active metabolite, varecoxib (a potent COX-2 inhibitor); parecoxib has a shorter plasma half-life (t1/2 = 0.6-0.8 hours), while varecoxib has a longer t1/2 (6-8 hours); after intravenous injection of 40 mg parecoxib, the peak plasma concentration of varecoxib is reached within 30 minutes, with a Cmax of 2.2-2.8 μg/mL; varecoxib is further metabolized by CYP3A4 and CYP2C9 Metabolized into inactive glucuronide conjugates, which are mainly excreted in urine (≈70%) and feces (≈20%) [2]
2. Distribution: The volume of distribution (Vd) of parecoxib is approximately 55-60 mL/kg; vardecoxib has a high plasma protein binding rate (≈98%) [2]

Protein binding
98%

---

1. Gastrointestinal toxicity: Unlike non-selective nonsteroidal anti-inflammatory drugs (NSAIDs), parecoxib (and its metabolite vardecoxib) does not significantly inhibit gastric COX-1 activity, and therefore has a low incidence of gastrointestinal mucosal damage; in long-term animal studies, rats were given 10-30 mg/kg of parecoxib daily for 6 months without inducing gastric ulcers, while aspirin (100 mg/kg/day) caused significant mucosal damage[2]
2. Cardiovascular safety: At therapeutic doses, parecoxib had no significant effect on blood pressure or heart rate in healthy subjects or postoperative patients; however, long-term high-dose administration (30 mg/kg/day for 12 months) in mice did not show a significant increase in adverse cardiovascular events, but caution is still needed for patients with a history of cardiovascular disease[2]
3. Nephrotoxicity: In short-term clinical use (≤72 hours), parecoxib had no significant effect on renal function (serum creatinine and glomerular filtration rate) in patients with normal renal function; animal studies showed that high-dose parecoxib (50 mg/kg/day for 2 weeks) did not cause significant renal histopathological changes [2]
4. Plasma protein binding rate: The plasma protein binding rate of vardecoxib (the active metabolite of parecoxib) is approximately 98%, while the plasma protein binding rate of parecoxib itself is approximately 95% [2]

[1]. Effect of parecoxib, a novel intravenous cyclooxygenase type-2 inhibitor, on the postoperative opioid requirement and quality of pain control. Anesthesiology.

[2]. [Selective inhibitors of cyclooxygenase-2 (COX-2), celecoxib and parecoxib: a systematic review]. Drugs Today (Barc). 2010 Feb;46 Suppl A:1-25.

[3]. Chronic administration of parecoxib exerts anxiolytic-like and memory enhancing effects and modulates synaptophysin expression in mice. BMC Anesthesiol. 2017 Nov 13;17(1):152.

[4]. Parecoxib inhibits glioblastoma cell proliferation, migration and invasion by upregulating miRNA-29c. Biol Open. 2017 Mar 15;6(3):311-316.

Parecoxib is an N-acylsulfonamide, formed by the condensation of vardicoxib and propionic acid, and is a prodrug of vardicoxib. It is a cyclooxygenase-2 inhibitor with dual functions as a non-narcotic analgesic, nonsteroidal anti-inflammatory drug, and prodrug. It belongs to the isoxazole class of compounds and is also an N-sulfonylformamide. Its function is related to that of vardicoxib. Parecoxib is a water-soluble injectable prodrug of vardicoxib, marketed in the EU under the brand name Dynastat. Parecoxib is a selective COX-2 inhibitor, belonging to the same class as celecoxib (Celebrex) and rofecoxib (Vioxx). Due to its injectability, it can be used perioperatively, especially for patients who cannot take oral medications. In most parts of Europe, parecoxib has been approved for short-term perioperative analgesia, similar to the use of torrential in the United States. The US Food and Drug Administration (FDA) issued a non-approval letter for parecoxib in 2005. Parecoxib is the amide prodrug of vardoxib, a cyclooxygenase II (COX-2) selective nonsteroidal anti-inflammatory drug (NSAID), and has anti-inflammatory, analgesic, and antipyretic effects. After administration, parecoxib is hydrolyzed by hepatic carboxylesterases to its active form, vardoxib. Vardoxib selectively binds to COX-2 and inhibits its activity, thereby preventing the conversion of arachidonic acid to prostaglandins, which are involved in the regulation of pain, inflammation, and fever. This NSAID does not inhibit COX-1 at therapeutic concentrations and therefore does not interfere with blood clotting.

---

Indications
For short-term perioperative pain control.

For short-term treatment of postoperative pain in adults.

For short-term treatment of postoperative pain. Whether to prescribe a selective COX-2 inhibitor should be based on an assessment of the patient's overall risk (see Sections 4.3 and 4.4).

For short-term treatment of postoperative pain.

---

1. Parecoxib (SC 69124) is the first selective COX-2 inhibitor administered parenterally for perioperative analgesia[1][2]
2. Its antitumor effect on glioblastoma is mediated by upregulation of miRNA-29c, which in turn inhibits matrix metalloproteinases (MMP-2/MMP-9) and the anti-apoptotic protein Bcl-2, thereby inhibiting cell proliferation, migration and invasion[4]
3. In mice, the anxiolytic-like and memory-enhancing effects of long-term parecoxib administration are associated with increased expression of synaptophysin in the hippocampus and prefrontal cortex. The cortex can enhance synaptic plasticity and neurotransmission in brain regions related to cognition and emotion[3]
4. Parecoxib is indicated for short-term (≤72 hours) treatment of postoperative pain in adults, with a recommended initial dose of 40 mg intravenously, followed by 20-40 mg intravenously every 6-12 hours as needed[1][2]

C19H18N2O4S

370.42222

370.098

198470-84-7

Parecoxib Sodium;198470-85-8;Parecoxib-d3

119828

White to off-white solid powder

1.3±0.1 g/cm3

148.9-151°

1.580

1.72

1

5

5

26

575

0

TZRHLKRLEZJVIJ-UHFFFAOYSA-N

InChI=1S/C19H18N2O4S/c1-3-17(22)21-26(23,24)16-11-9-14(10-12-16)18-13(2)25-20-19(18)15-7-5-4-6-8-15/h4-12H,3H2,1-2H3,(H,21,22)

N-[4-(5-methyl-3-phenyl-1,2-oxazol-4-yl)phenyl]sulfonylpropanamide

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 : ≥ 50 mg/mL (~134.98 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.75 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.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (6.75 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.

---

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