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Chemotherapeutic properties of phospho-nonsteroidal anti-inflammatory drugs, a new class of anticancer compounds.
The findings show the strong anticancer efficacy and promising safety of phospho-NSAIDs in preclinical models of breast, colon, and pancreatic cancer, suggesting further evaluation as anticancer agents.
The novel phospho‐non‐steroidal anti‐inflammatory drugs, OXT‐328, MDC‐22 and MDC‐917, inhibit adjuvant‐induced arthritis in rats
Three novel modified NSAIDs are evaluated for the anti‐inflammatory efficacy and safety in rheumatoid arthritis: phospho‐aspirin,ospho‐ibuprofen and phospho-sulindac.
Regioselective oxidation of phospho‐NSAIDs by human cytochrome P450 and flavin monooxygenase isoforms: implications for their pharmacokinetic properties and safety
- G. Xie, C. Wong, Ka-Wing Cheng, Liqun Huang, P. Constantinides, B. Rigas
- Biology, MedicineBritish journal of pharmacology
- 1 September 2012
Phospho‐ibuprofen and phospho‐sulindac metabolism by major human cytochrome P450s (CYPs) and flavin monooxygenases (FMOs) is investigated.
Phospho-Ibuprofen (MDC-917) Is a Novel Agent against Colon Cancer: Efficacy, Metabolism, and Pharmacokinetics in Mouse Models
The results provide a pharmacological basis to explain, at least in part, the anticancer efficacy and safety of this promising compound and indicate that PI merits further evaluation as an anticancer agent.
Phospho-Sulindac (OXT-328) Combined with Difluoromethylornithine Prevents Colon Cancer in Mice
P-S/DFMO is an efficacious drug combination for colon cancer prevention and also show the safety of P-S, which may overcome the limiting side effects of conventional sulindac.
Phospho-sulindac (OXT-922) inhibits the growth of human colon cancer cell lines: a redox/polyamine-dependent effect.
OXT-922 possesses promising anticancer properties and deserves further evaluation, and enhanced spermidine/spermine N(1)-acetyltransferase activity, reduced the cellular polyamine content and synergized with difluoromethylornithine to inhibit cancer cell proliferation and induce apoptosis.
Phospho-NSAIDs Have Enhanced Efficacy in Mice Lacking Plasma Carboxylesterase: Implications for their Clinical Pharmacology
Investigation of the metabolism, pharmacokinetics and efficacy of phospho-NSAIDs in Ces1c-knockout mice indicates that intact phospho/sulindac are the pharmacologically active entities andospho- NSAIDs are expected to be more efficacious in humans than in rodents due to their differential expression of carboxylesterases.
Phospho-sulindac (OXT-328), a novel sulindac derivative, is safe and effective in colon cancer prevention in mice.
BACKGROUND & AIMS Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective cancer chemopreventive agents. However, chronic administration of NSAIDs is associated with significant side effects,…
Carboxylesterases 1 and 2 Hydrolyze Phospho-Nonsteroidal Anti-Inflammatory Drugs: Relevance to Their Pharmacological Activity
- C. Wong, Ka-Wing Cheng, B. Rigas
- Biology, ChemistryJournal of Pharmacology and Experimental…
- 1 February 2012
Results show that carboxylesterase mediates that metabolic inactivation of phospho-NSAIDs, and the inhibition of carboxyleterases improves the efficacy of phosphate- NSAIDs in vitro and in vivo.
The metabolism and pharmacokinetics of phospho‐sulindac (OXT‐328) and the effect of difluoromethylornithine
Phospho‐sulindac prevents colon cancer in mice, especially when combined with difluoromethylornithine (DFMO) and here, its metabolism and pharmacokinetics are explored.