Disease relevance of C11705

• PGI2 is produced by COX-2 and a selective inhibitor of this enzyme, SC-58125, also significantly reduced the increases in plasma renin activity and renin mRNA expression in WT mice with renal artery stenosis, but these effects were absent in IP-/- mice [1].
• SC-58125, a structural analog of the Cox-2-selective inhibitor Celebrex reduced by approximately 70% human memory B cell differentiation to HPV 16 VLP IgG-secreting cells [2].
• In this study, human colorectal carcinoma HCT-116 cells were treated with the Cox-1 specific inhibitor SC-560 and the Cox-2 specific inhibitor SC-58125 to evaluate their ability to induce apoptosis, inhibit cell proliferation, inhibit growth on soft agar and modulate gene expression [3].
• However, the repetitive epicutaneous administration of SC-58125 substantially and significantly suppressed papilloma development [4].
• TPA-induced edema formation, epidermal DNA synthesis, and mitotic activity were not impaired by SC-58125 applied at a dose that inhibited TPA-induced prostaglandin E2 synthesis [4].

High impact information on C11705

• Serum IL-6 and paw IL-6 mRNA levels were also reduced to near normal levels by SC-58125 [5].
• Two specific COX-2 inhibitors, SC-58125 and NS 398, also, in a dose-dependent manner, attenuate baseline and type alpha transforming growth factor-stimulated mitogenesis, although PG levels are decreased > 90% at all concentrations of inhibitor tested [6].
• The IL-1beta-induced increase in the release of PGH2 by HUVECs was suppressed by the COX-2-selective inhibitor SC-58125 and correlated with both COX-2 expression and PGIS inactivation [7].
• A new class of compounds has recently been developed (SC-58125) that have a high degree of selectivity for the inducible form of cyxlooxygenase (COX-2) over the constitutive form (COX-1) [8].
• SC-58125 moderately induced apoptosis and inhibited growth on soft agar at higher concentrations than were required for SC-560 [3].

Biological context of C11705

• Substitutions of COX-1 sequences in COX-2 at the mouth of the active site of COX-2 did not change the selectivity of SC-58125 [8].
• When cells were preincubated with inhibitors to allow time-dependent inhibition prior to arachidonic acid stimulation, NS-398, CGP 28238, L-745,337, SC-58125 all behaved as potent (IC50 = 1-30 nM) and selective inhibitors of PGHS-2, in contrast to indomethacin, flurbiprofen or diclofenac which are potent inhibitors of enzymes [9].
• We conclude that SC-58125 primarily exerts a cytostatic effect in vivo, which is likely to be mediated through inhibition of progression through the G(2)/M phase of the cell cycle [10].
• Cell proliferation ((3)H-thymidine uptake) was significantly inhibited by NS-398 and SC-58125, the EP(1) antagonist SC-51322, AH6809 (EP(1)/EP(2) antagonist), and the EP(4) antagonist AH23848B, but was not affected by exogenous PGE(2) [11].

Anatomical context of C11705

• 4. SC-58125 did not significantly affect leukocyte infiltration into the airpouch at any dose tested (up to 10 mg kg(-1)) [12].
• In both cell lines [3H]thymidine incorporation stimulated by serum was inhibited by the COX-2 inhibitor SC-58125, but not by the COX-1 inhibitor VSA [13].

Associations of C11705 with other chemical compounds

• However, inter-helical distances calculated and determined by EPR for PGHS-2 complexed with arachidonic acid, flurbiprofen, and SC-58125 were in close agreement with those obtained from the cognate crystal structures [14].
• Finally, SC-58125 and dexamethasone reduced the growth inhibitory effect of ET-1 and TNF-alpha, indicating that activation of COX-2 is required for inhibition of HSC proliferation [15].
• PGE2 synthesis was significantly reduced by compound SC-58125, a specific COX-2 inhibitor [16].
• Rats were treated with the COX-1/COX-2 inhibitor indomethacin and the selective COX-2 inhibitors meloxicam and SC 58125 [17].
• However, ascorbic acid had no synergistic effect along with other COX inhibitors (SC-58125 and indomethacin) [18].

Gene context of C11705

• Additional rats received Pio (10 mg.kg-1.day-1) for 3 days and intravenous SC-58125 [a cyclooxygenase-2 (COX-2) inhibitor] or SC-560 (a COX-1 inhibitor) 15 min before ischemia [19].
• Unstimulated and stimulated cells were exposed to the specific COX-1 inhibitor valerylsalicylic acid (VSA) and the COX-2 inhibitors NS-398 and SC-58125 [20].
• The effects of serum on proliferation were then evaluated in the presence of the COX-1 inhibitor, valerylsalicyclic acid (VSA), the COX-2 inhibitor, SC-58125, or indomethacin [13].
• SC-58125, a selective inhibitor of COX-2, has a potent apoptosis inducing effect [13].
• Low concentrations of indomethacin and valerylsalicylic acid (VSA) were evaluated as cyclooxygenase-1 inhibitors and their effects compared with the effects of a specific cyclooxygenase-2 inhibitor, SC-58125 [21].

Analytical, diagnostic and therapeutic context of C11705

• These results indicate that aberrant expression of PGHS-2 in epidermal tumors may be a relevant target for prevention of epidermal cancer development in experimental animals and that the PGHS-2-specific inhibitor SC-58125, which is a potent inhibitor of tumor promotion in mouse skin, may be important for cancer chemoprevention in humans as well [4].
• A cyclooxygenase-2 inhibitor (SC-58125) blocks growth of established human colon cancer xenografts [10].

References