IC50: 0.009 μM for COX-1; 6.3 μM for COX-2
SC-560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trif luoromethylpyrazole] is a COX-1-selective inhibitor, which can be used as a pharmacological tool to study the role of COX-1-derived PGs in inflammation and pain. COX-1 is an enzyme that is responsible for formation of prostanoids, including thromboxane and prostaglandins.
In vitro: Preincubation of COX-1 with SC-560 inhibited the conversion of arachidonic acid to PGE2 in a concentration-dependent manner [1]. SC-560 was necessary to sustain a reduced basal level of PGI2 for an extended period. SC-560 inhibits cell proliferation and accelerates apoptosis which results in attenuated tumor growth [2].
In vivo: Oral dosing with either 10 or 30 mg/kg SC-560 1 hr before assay completely inhibited COX-1-derived platelet thromboxane B2, gastric PGE2, and dermal PGE2 production [1]. SC-560 can suppress ovarian surface epithelial tumor growth. Tumor growth was suppressed in allografted mice treated with SC-560 for a longer period, but the reduction in tumor growth was less dramatic than the short-term treated [2].
Clinical trial: So far, no clinical study has been conducted.
References:
[1] Daikoku T, Wang D, Tranguch S, Morrow JD, Orsulic S, DuBois RN, Dey SK. Cyclooxygenase-1 is a potential target for prevention and treatment of ovarian epithelial cancer. Cancer Res. 2005 May 1;65(9):3735-44.
[2] Christopher J. Smith, Yan Zhang, Carol M. Koboldt, Jerry Muhammad, Ben S. Zweifel, Alex Shaffer, John J. Talley, Jaime L. Masferrer, Karen Seibert, Peter C. Isakson. Pharmacological analysis of cyclooxygenase-1 in inflammation. Proc Natl Acad Sci U S A. 1998 Oct 27; 95(22): 13313–13318.