SC 560 is a potent inhibitor of COX enzymes, with IC50 values of 0.009μM and 6.3µM for COX-1 and COX-2, respectively[1]. SC 560 inhibits PGE2 and thromboxane A2 synthesis in monocytes and platelets with IC50 values of 1.8nM and 2.5nM, respectively[2]. By inhibiting COX-1, SC 560 suppresses the production of thromboxane A2 in platelets and reduces intimal hyperplasia[3]. SC 560 has been widely used in tumor research to inhibit the growth of various types of cancer cells[4].
In vitro, SC 560 treatment for 3 days inhibited the replication of bovine viral diarrhea virus (BVDV) in Mardin-Darby bovine kidney (MDBK) cells, with an EC50 value of 10.9µM[5]. Treatment with 80µM SC 560 for 24 hours reduced the proliferation of HT-29 cells, induced G0/G1 phase cell cycle arrest, and downregulated proteins related to the G1-S phase transition[6]. Incubation with 40µM SC 560 for 24 hours induced apoptosis in HuH-6 cells, decreased the levels of anti-apoptotic proteins survivin and XIAP, and activated caspase-3 and caspase-7[7].
In vivo, SC 560 treatment via intraperitoneal injection at a dose of 3mg/kg/day for 14 days, alleviated liver fibrosis and pulmonary inflammation in cirrhotic rats with hepatopulmonary syndrome, reduced mean arterial pressure and portal venous pressure, and mitigated hypoxemia and pulmonary shunting[8]. Oral administration of SC 560 (3mg/kg) twice daily for 21 days inhibited tumor growth and angiogenesis in the SKOV-3 xenograft mouse model[9].
References:[1] Smith C J, Zhang Y, Koboldt C M, et al. Pharmacological analysis of cyclooxygenase-1 in inflammation[J]. Proceedings of the National Academy of Sciences, 1998, 95(22): 13313-13318.
[2] Brenneis C, Maier T J, Schmidt R, et al. Inhibition of prostaglandin E2 synthesis by SC‐560 is independent of cyclooxygenase 1 inhibition[J]. The FASEB Journal, 2006, 20(9): 1352-1360.
[3] Connolly E, Bouchier-Hayes D J, Kaye E, et al. Cyclooxygenase isozyme expression and intimal hyperplasia in a rat model of balloon angioplasty[J]. The Journal of Pharmacology and Experimental Therapeutics, 2002, 300(2): 393-398.
[4] Lee E, Choi M K, Youk H J, et al. 5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole acts in a reactive oxygen species-dependent manner to suppress human lung cancer growth[J]. Journal of cancer research and clinical oncology, 2006, 132(4): 223-233.
[5] Okamoto M, Sakai M, Goto Y, et al. Anti-bovine viral diarrhoea virus and hepatitis C virus activity of the cyclooxygenase inhibitor SC-560[J]. Antiviral Chemistry and Chemotherapy, 2009, 20(1): 47-54.
[6] Wu W K K, Sung J J Y, Wu Y C, et al. Inhibition of cyclooxygenase-1 lowers proliferation and induces macroautophagy in colon cancer cells[J]. Biochemical and biophysical research communications, 2009, 382(1): 79-84.
[7] Lampiasi N, Foderà D, D'Alessandro N, et al. The selective cyclooxygenase-1 inhibitor SC-560 suppresses cell proliferation and induces apoptosis in human hepatocellular carcinoma cells[J]. International journal of molecular medicine, 2006, 17(2): 245-252.
[8] Chang C C, Lee W S, Hsieh H G, et al. Selective cyclooxygenase inhibition by SC-560 improves hepatopulmonary syndrome in cirrhotic rats[J]. Plos one, 2017, 12(6): e0179809.
[9] Li W, Wan L, Zhai L Y, et al. Effects of SC-560 in combination with cisplatin or taxol on angiogenesis in human ovarian cancer xenografts[J]. International Journal of Molecular Sciences, 2014, 15(10): 19265-19280.