Mechanism of Inhibition of Novel Cox-2 Inhibitors

Gierse, James K.; Kurumbail, Ravi G.; Walker, Mark C.; Hood, Bill; Monahan, Joe; Pawlitz, Jennifer L.; Stegeman, Rick; Stevens, Anna M.; Kiefer, Jim; Koboldt, Carol M.; Moreland, Kirby T.; Rowlinson, Scott W.; Marnett, L.J.; Pierce, Jennifer L.; Carter, Jeff; Talley, John J.; Isakson, Peter C.; Seibert, Karen

doi:10.1007/978-1-4615-0193-0_56

Cited by 7 publications

(4 citation statements)

References 5 publications

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“…3a and b) that probably reflects both mass density and conformational alterations upon formation of the holoprotein. The addition of the COX-2 selective inhibitor, celecoxib, at concentrations expected to saturate the active site (IC 50 ∼0.03 M [31]) produced further PWR spectral changes ( Fig. 3c and d), again due to both mass density and conformational changes accompanying ligand binding.…”

Section: Binding Of Inhibitors To Cox-1 and -2mentioning

confidence: 89%

“…Furthermore, sufficient COX-1 was present on the PWR resonator to produce spectral shifts (Fig. 4) upon addition of a saturating amount of a COX-1 specific inhibitor, SC-560 (IC 50 ∼0.0005 M [31]). This result clearly demonstrates that PWR experiments can be performed using membrane preparations obtained from cells over expressing recombinant proteins, without the necessity of extensive isolation and purification.…”

Section: Binding Of Inhibitors To Cox-1 and -2mentioning

confidence: 99%

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Plasmon-waveguide resonance spectroscopy applied to three potential drug targets: cyclooxygenase-2, hepatitis C virus RNA polymerase and integrin αVβ3

Devanathan

Walker

Salamon

et al. 2004

Journal of Pharmaceutical and Biomedical Analysis

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Section: Binding Of Inhibitors To Cox-1 and -2mentioning

confidence: 89%

Section: Binding Of Inhibitors To Cox-1 and -2mentioning

confidence: 99%

Plasmon-waveguide resonance spectroscopy applied to three potential drug targets: cyclooxygenase-2, hepatitis C virus RNA polymerase and integrin αVβ3

Devanathan

Walker

Salamon

et al. 2004

Journal of Pharmaceutical and Biomedical Analysis

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“…Most of the commonly used NSAIDs have high selectivity to COX-1 more than COX-2. Therefore, their use for long time will cause gastric irritation, ulcer or bleeding [ 6 ]. The selective inhibition of COX-2 will have the same anti-inflammatory effect as the non-selective inhibitors but with less gastrointestinal adverse effect incidence.…”

Section: Introductionmentioning

confidence: 99%

Indole Derivatives as Cyclooxygenase Inhibitors: Synthesis, Biological Evaluation and Docking Studies

et al. 2018

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A new series of 2-(5-methoxy-2-methyl-1H-indol-3-yl)-N′-[(E)-(substituted phenyl) methylidene] acetohydrazide derivatives (S1–S18) were synthesized and evaluated for their anti-inflammatory activity, analgesic activity, ulcerogenic activity, lipid peroxidation, ulcer index and cyclooxygenase expression activities. All the synthesized compounds were in good agreement with spectral and elemental analysis. Three synthesized compounds (S3, S7 and S14) have shown significant anti-inflammatory activity as compared to the reference drug indomethacin. Compound S3 was further tested for ulcerogenic index and cyclooxygenase (COX) expression activity. It was selectively inhibiting COX-2 expression and providing the gastric sparing activity. Docking studies have revealed the potential of these compounds to bind with COX-2 enzyme. Compound S3 formed a hydrogen bond between OH of Tyr 355 and NH2 of Arg 120 with carbonyl group and this hydrogen bond was similar to that formed by indomethacin. This study provides insight for compound S3, as a new lead compound as anti-inflammatory agent and selective COX-2 inhibitor.

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“…Children with JRA are often candidates for nonsteroidal anti‐inflammatory drug (NSAID) therapy because pain is common. Celecoxib is an NSAID that exhibits anti‐inflammatory, analgesic, and antipyretic activities by inhibiting prostaglandin synthesis, primarily via inhibition of cyclooxygenase‐2 (COX‐2) but not COX‐1 at therapeutic concentrations in humans 2 . Along with several adult indications, celecoxib is currently approved by the US Food and Drug Administration (FDA) for the treatment of JRA in children (aged ≥2 years).…”

mentioning

confidence: 99%

Dosing Celecoxib in Pediatric Patients With Juvenile Rheumatoid Arthritis

Krishnaswami

Hutmacher²,

Robbins

et al. 2012

The Journal of Clinical Pharma

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The objective was to derive dosing recommendations for the use of celecoxib in patients with juvenile rheumatoid arthritis (JRA) using pharmacokinetic (PK) and exposure-response data. PK and efficacy data from a randomized, double-blind, 12-week study of celecoxib dosed at 3 and 6 mg/kg twice a day (bid) as an investigational suspension formulation in 152 JRA patients aged 2 to 17 years, PK data from 36 adult RA patients, and relative bioavailability data in healthy adults comparing suspension or capsule sprinkles with the commercial capsule were analyzed. Typical oral clearance (L/h) values were 40% and 24% lower in patients weighing 10 and 25 kg, respectively, compared with a 70-kg patient. Longitudinal, logistic pharmacodynamic models incorporating linear effects of dose/area under the plasma concentration-time curve (AUC) over 0 to 12 hours (AUC(0-12)) suggested that the percentage of responders increased with celecoxib exposure. Systemic exposures (AUC) were similar for the suspension, capsule sprinkles, and intact capsule. Administration of a 50-mg bid capsule (or sprinkles) for patients weighing 10 to 25 kg and 100 mg bid for patients >25 kg was predicted to yield similar exposures and response rates as those observed in the JRA trial. Doses and dosage forms not studied in the JRA trial were approved based on the results of this analysis.

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Mechanism of Inhibition of Novel Cox-2 Inhibitors

Cited by 7 publications

References 5 publications

Plasmon-waveguide resonance spectroscopy applied to three potential drug targets: cyclooxygenase-2, hepatitis C virus RNA polymerase and integrin αVβ3

Plasmon-waveguide resonance spectroscopy applied to three potential drug targets: cyclooxygenase-2, hepatitis C virus RNA polymerase and integrin αVβ3

Indole Derivatives as Cyclooxygenase Inhibitors: Synthesis, Biological Evaluation and Docking Studies

Dosing Celecoxib in Pediatric Patients With Juvenile Rheumatoid Arthritis

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