Cell experiment:

HuH-6 and HA22T/VGH cells (5000/well) are treated with various concentrations of SC-560 (5, 10, 25, 50, 100, 200 μM) and cultured for 72 h. At the end of treatment, cell viability is assessed by MTS assay[2].

Animal experiment:

Rats: The pharmacokinetics of SC-560 is studied in Sprague-Dawley rats after a single intravenous (i.v.) and oral dose (10 mg/kg) in polyethylene glycol (PEG) 600 and a single oral dose (10 mg/kg) in 1% methylcellulose (MC). Serial blood samples are collected via a catheter inserted in the right jugular vein and serum samples are analysed for SC-560 using reverse phase HPLC. After oral administration of SC-560 in PEG, urine is also collected for 24 h and analyzed for urinary sodium, chloride, and potassium as well as NAG[3].

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.