Tolfenamic acid-d4 is intended for use as an internal standard for the quantification of tolfenamic acid by GC- or LC-MS. Tolfenamic acid is a non-steroidal anti-inflammatory drug (NSAID) with anticancer activity.1,2,3,4,5 It is selective for COX-2 over COX-1 in canine DH82 monocyte/macrophage cells (IC50s = 3.53 and >51.2 μg/ml, respectively).1 Tolfenamic acid inhibits calcium influx in human polymorphonuclear leukocytes (PMNLs) induced by N-formyl-L-methionyl-L-leucyl-L-phenylalanine or the calcium ionophore A23187 in a concentration-dependent manner.2 It decreases protein levels of the transcription factors Sp1, Sp3, and Sp4 in PANC-1 and L3.6pl cells when used at a concentration of 50 μM and inhibits proliferation of PANC-1, L3.6pl, and PANC-28 cells in a concentration-dependent manner.4 Tolfenamic acid (50 and 100 μM) decreases the viability of and induces apoptosis in MDA-MB-231 cells.5 It reduces tumor growth in an MDA-MB-231 mouse xenograft model when administered at doses of 25 and 50 mg/kg. Tolfenamic acid (150 μmol/kg) reduces carrageenan-induced paw edema in mice by 24%.3

|1. Kay-Mugford, P., Benn, S.J., LaMarre, J., et al. In vitro effects of nonsteroidal anti-inflammatory drugs on cyclooxygenase activity in dogs. Am. J. Vet. Res. 61(7), 802-810 (2000).|2. Kankaanranta, H., and Moilanen, E. Flufenamic and tolfenamic acids inhibit calcium influx in human polymorphonuclear leukocytes. Mol. Pharmacol. 47(5), 1006-1013 (1995).|3. Galanakis, D., Kourounakis, A.P., Tsiakitzis, K.C., et al. Synthesis and pharmacological evaluation of amide conjugates of NSAIDs with L-cysteine ethyl ester, combining potent antiinflammatory and antioxidant properties with significantly reduced gastrointestinal toxicity. Bioorg. Med. Chem. Lett. 14(14), 3639-3643 (2004).|4. Abdelrahim, M., Baker, C.H., Abbruzzese, J.L., et al. Tolfenamic acid and pancreatic cancer growth, angiogenesis, and Sp protein degradation. J. Natl. Cancer Inst. 98(12), 855-868 (2006).|5. Kim, H.J., Cho, S.D., Kim, J., et al. Apoptotic effect of tolfenamic acid on MDA-MB-231 breast cancer cells and xenograft tumors. J. Clin. Biochem. Nutr. 52(1), 21-26 (2013).