CAY10404

CAY10404 is a potent and highly selective cyclooxygenase-2 (COX-2) inhibitor with an IC50 of 1 nM. CAY10404 exhibits no inhibition of COX-1 (IC50>500 µM)[1]. CAY10404 is a potent inhibitor of PKB/Akt and MAPK signaling pathways and induces apoptosis in NSCLC cells. CAY10404, a diarylisoxazole, has good analgesic, anti-inflammatory, and anti-cancer activities[2][3].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> PI3K/Akt/mTOR >> Akt

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Immunology/Inflammation >> COX

Research Areas >> Neurological Disease

COX-2:1 nM (IC50)

COX-1:>500 μM (IC50)

Akt

CAY10404 is a potent and selective COX-2 inhibitor with a selectivity index (SI; COX-1 IC50/COX-2 IC50) of >500000[1]. CAY10404 (10-100 µM; for 3 days) inhibits the growth of NSCLC cell lines in a concentration-dependent manner and has an average 50% inhibitory concentration (IC50) of 60-100 µM[3]. CAY10404 (20-100 µM; for 3 days) induces apoptosis in NSCLC cells[3]. CAY10404 (80 µM; for 3 days) induces a concentration-dependent decrease in the level of the anti-apoptotic proteins (Bcl-2 and Bcl-XL) and pAkt and pGSK-3β[3]. CAY10404 (20, 50, 80, 100 µM; for 14 days) compromises the ability of H460 cells to form colonies in anchorage-independent growth in a concentration-dependent manner[3]. Cell Viability Assay[3] Cell Line: Non-small cell lung cancer (NSCLC) cells (H-1703, H-358, H-460) Concentration: 10-100 µM Incubation Time: For 3 days Result: Inhibited the growth of NSCLC cell lines in a concentration-dependent manner. Apoptosis Analysis[3] Cell Line: H460 cells Concentration: 20, 50, 100 µM Incubation Time: For 3 days Result: Induced apoptosis in NSCLC cells. Western Blot Analysis[3] Cell Line: NSCLC cells (H-358, H-460) Concentration: 80 µM Incubation Time: For 3 days Result: Induced a concentration-dependent decrease in the level of the anti-apoptotic proteins (Bcl-2 and Bcl-XL) and pAkt and pGSK-3β, without changing the level of the pro-apoptotic protein (Bax) and total Akt and GSK-3β protein levels.

CAY10404 (50 mg/kg/day; ip; for 4 days) decreases lung inflammation in HTV mice and attenuates ventilator-induced lung injury[2]. Animal Model: Adult male C57Bl/6J mice weighing 24-30 g[2] Dosage: 50 mg/kg Administration: IP; daily; for 4 days Result: Attenuated cyclooxygenase activity, significantly decreasing BAL PGE2 and 6-keto PGF1α. Decreased lung inflammation in HTV mice (high tidal volume; 20 ml/kg; for 4 hours) and attenuates ventilator-induced lung injury.

[1]. A G Habeeb, et al. Design and synthesis of 4,5-diphenyl-4-isoxazolines: novel inhibitors of cyclooxygenase-2 with analgesic and antiinflammatory activity. J Med Chem. 2001 Aug 30;44(18):2921-7.

[2]. Joshua A Robertson, et al. The role of cyclooxygenase-2 in mechanical ventilation-induced lung injury. Am J Respir Cell Mol Biol. 2012 Sep;47(3):387-94.

[3]. Yongseon Cho, et al. Effects of CAY10404 on the PKB/Akt and MAPK pathway and apoptosis in non-small cell lung cancer cells. Respirology. 2009 Aug;14(6):850-8.