celecoxib

Celecoxib (SC 58635) is a Nonsteroidal Anti-inflammatory Drug. The mechanism of action of celecoxib is as a Cyclooxygenase Inhibitor.

Demethyl celecoxib is a selective inhibitor of COX-2 with anti-inflammatory activity (IC50 of 32 nM). with anti-inflammatory activities. Desmethyl Celecoxib is an analog of Celecoxib and with the optimal yield of 75%.

2,5-dimethyl Celecoxib is a derivative of celecoxib that does not inhibit COX-2 (IC50 = >100 μM).1 It does inhibit microsomal prostaglandin E synthase-1 (mPGES-1) in HeLa cells (IC50 = 15.6 μM) and reduces prostaglandin E2 production in HeLa, A549, and HCA-7 cells (IC50s = 0.64, 0.83, and 3.08 μM, respectively).2 It inhibits proliferation of drug-sensitive RPMI8226 and multidrug-resistant 8226 Dox40 multiple myeloma cells, as well as increases the rate of apoptosis when used at concentrations of 20 and 30 μM.3 2,5-dimethyl Celecoxib reduces the expression of survivin, cyclin A, cyclin B, MEK1, and MEK2 in 8226 Dox40 cells. The antiproliferative effect of 2,5-dimethyl celecoxib is independent of mPGES-1 inhibition.2References1. Zhu, J., Song, X., Lin, H.-P., et al. Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents. J. Natl. Cancer Inst. 94(23), 1745-1757 (2002).2. Wobst, I., Schiffmann, S., Birod, K., et al. Dimethylcelecoxib inhibits prostaglandin E2 production. Biochem. Pharmacol. 76(1), 62-69 (2008).3. Kardosh, A., Soriano, N., Liu, Y.-T., et al. Multitarget inhibition of drug-resistant multiple myeloma cell lines by dimethyl-celecoxib (DMC), a non-COX-2 inhibitory analog of celecoxib. Blood 106(13), 4330-4338 (2005). 2,5-dimethyl Celecoxib is a derivative of celecoxib that does not inhibit COX-2 (IC50 = >100 μM).1 It does inhibit microsomal prostaglandin E synthase-1 (mPGES-1) in HeLa cells (IC50 = 15.6 μM) and reduces prostaglandin E2 production in HeLa, A549, and HCA-7 cells (IC50s = 0.64, 0.83, and 3.08 μM, respectively).2 It inhibits proliferation of drug-sensitive RPMI8226 and multidrug-resistant 8226 Dox40 multiple myeloma cells, as well as increases the rate of apoptosis when used at concentrations of 20 and 30 μM.3 2,5-dimethyl Celecoxib reduces the expression of survivin, cyclin A, cyclin B, MEK1, and MEK2 in 8226 Dox40 cells. The antiproliferative effect of 2,5-dimethyl celecoxib is independent of mPGES-1 inhibition.2 References1. Zhu, J., Song, X., Lin, H.-P., et al. Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents. J. Natl. Cancer Inst. 94(23), 1745-1757 (2002).2. Wobst, I., Schiffmann, S., Birod, K., et al. Dimethylcelecoxib inhibits prostaglandin E2 production. Biochem. Pharmacol. 76(1), 62-69 (2008).3. Kardosh, A., Soriano, N., Liu, Y.-T., et al. Multitarget inhibition of drug-resistant multiple myeloma cell lines by dimethyl-celecoxib (DMC), a non-COX-2 inhibitory analog of celecoxib. Blood 106(13), 4330-4338 (2005).

Celecoxib carboxylic acid is an inactive metabolite of the COX-2 inhibitor celecoxib .1,2It is formed from celecoxib primarily by the cytochrome P450 (CYP) isoform CYP2C9. 1.Liu, H., Huang, X., Shen, J., et al.Inhibitory mode of 1,5-diarylpyrazole derivatives against cyclooxygenase-2 and cyclooxygenase-1: Molecular docking and 3D QSAR analysesJ. Med. Chem.45(22)4816-4827(2002) 2.Kim, S.-H., Kim, D.-H., Byeon, J.-Y., et al.Effects of CYP2C9 genetic polymorphisms on the pharmacokinetics of celecoxib and its carboxylic acid metaboliteArch. Pharm. Res.40(3)382-390(2017)

Celecoxib carboxylic acid acyl-β-D-glucuronide is a phase II metabolite of celecoxib . Celecoxib is an anti-inflammatory compound from the diaryl heterocycle class that selectively inhibits cyclooxygenase-2 (COX-2; IC50s = 22.9 and 0.05 μM for COX-1 and COX-2, respectively). Celecoxib carboxylic acid acyl-β-D-glucuronide is a minor metabolite, accounting for 2% of the administered dose in human urine and rat bile.

Hydroxy celecoxib, an inactive metabolite of celecoxib, is synthesized through the metabolism of celecoxib by cytochrome P450 (CYP) isoforms CYP2C9, CYP3A4, and CYP2D6 in human liver microsomes.

Osu03012 (AR-12) is an orally bioavailable, small-molecule, celecoxib-derived inhibitor of phosphoinositide-dependent kinase-1 (PDK1) with potential antineoplastic activity.

Parecoxib is a cyclooxygenase-2 inhibitor used for the short-term treatment of postoperative pain in adults. Parecoxib is a water-soluble and injectable prodrug of valdecoxib. Parecoxib is a COX2 selective inhibitor in the same category as celecoxib and r

COX-2-IN-7 (compound 4a) is a potent and selective COX-2 inhibitor with greater selectivity than Celecoxib and an IC50 value of 6.585 µM. It exhibits good anti-inflammatory properties and low ulcerogenic activity in vivo[1].

COX-2 5-LOX-IN-1 (compound 3a), a benzothiophen-2-yl pyrazole carboxylic acid derivative, is a potent dual inhibitor of COX-2 and 5-LOX, exhibiting superior analgesic and anti-inflammatory properties compared to Celecoxib and Indomethacin. It demonstrates strong inhibitory activity against COX-1, COX-2, and 5-LOX, with IC50 values of 12.13 μM, 0.4 μM, and 4.96 μM, respectively [1].

COX-2-IN-18 (Compound 3) is a highly effective COX-2 inhibitor with an IC50 value of 0.775 μM, demonstrating strong inhibitory activity against COX-2. Its potency is comparable to the reference drug Celecoxib (IC50 = 0.153 μM), showing promise in the field of cancer research [1].

COX-2 5-LOX-IN-2 is a benzothiophen-2-ylpyrazole carboxylic acid derivative that inhibits both COX-2 and 5-LOX. COX-2 5-LOX-IN-2 (5b) has IC50 values of 5.40, 0.01, and 1.78 μM for COX-1, COX-2, and 5-LOX, respectively, and exhibits greater analgesic and anti-inflammatory activities than Celecoxib and Indomethacin.

COX-2-IN-8 (Compound 6a) is a potent, selective, orally active COX-2 inhibitor (IC50: 6.585 μM) with a higher COX-2 selectivity than Celecoxib.

COX-2-IN-9 is a selective, potent, orally active COX-2 inhibitor (IC50: 10.17 μM).COX-2-IN-9 has a higher COX-2 selectivity than Celecoxib.COX-2-IN-9 exhibits good in vivo anti-inflammatory activity and low ulcerogenic effect.

R-130823 is a ighly selective inhibition against mitogen-activated protein kinase p38alpha (IC50=22 nM). The release of tumor necrosis factor-alpha, interleukin-1beta, -6 and -8 was inhibited in lipopolysaccharide-stimulated human blood pretreated by R-130823 , with IC50 values of 0.089, 0.066, 0.95 and 0.16 microM, respectively. R-130823 reduced the established hind paw swelling in rat adjuvant-induced arthritis, while methotrexate showed no suppression. In the same model, R-130823 ameliorated adjuvant-induced hyperalgesia with rapid onset and long duration comparable to a cyclooxygenase-2 inhibitor, celecoxib.

COX-1 2-IN-8 (compound 11f) is an orally active inhibitor of both COX-1 and COX-2, with IC50 values of 2.14 µM and 0.58 µM, respectively. Its anti-inflammatory activity surpasses that of celecoxib.