SC-560

Names

[ Name ]:
SC-560

[Synonym ]:
Ionomycin calcium salt
Lopac-S-2064
5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole
1H-Pyrazole, 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-
5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl pyrazole
SC560
SC-560

Biological Activity

[Description]:

SC-560 is a potent and selective COX-1 inhibitor with an IC50 of 9 nM.

[Related Catalog]:

Research Areas >> Cancer

[Target]

COX-1:9 nM (IC50)

COX-2:6.3 μM (IC50)

[In Vitro]

Preincubation of COX-1 with SC-560 inhibits the conversion of arachidonic acid to PGE2 in a concentration-dependent manner. The IC50 of SC-560 for COX-2 is 6.3 μM, nearly 1,000-fold higher than with COX-1[1]. SC-560 shows a dose and time dependent inhibitory effect on HCC cell growth. SC-560 also inhibits colony formation in soft agar and induces apoptosis in HCC cells in a dose-dependent manner. Moreover, SC-560 decreases the levels of the anti-apoptotic proteins survivin and XIAP and activates caspase 3 and 7 in a dose and time dependent fashion[2].

[In Vivo]

Oral dosing with either 10 or 30 mg/kg SC-560 1 hour before assay completely inhibits ionophore-stimulated TxB2production, indicating that SC-560 is orally bioavailable and inhibits COX-1 in vivo[1]. SC-560 extensively distributes into rat tissues, and has a CL approaching hepatic plasma flow. The drug displays low less than 15% and formulation dependent bioavailability after oral administration and demonstrates kidney toxicity[3].

[Cell Assay]

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 admin]

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].

[References]

[1]. Smith CJ, et al. Pharmacological analysis of cyclooxygenase-1 in inflammation. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13313-8.

[2]. Lampiasi N, et al. The selective cyclooxygenase-1 inhibitor SC-560 suppresses cell proliferation and induces apoptosis in human hepatocellular carcinoma cells. Int J Mol Med. 2006 Feb;17(2):245-52.

[3]. Teng XW, et al. Formulation dependent pharmacokinetics, bioavailability and renal toxicity of a selective cyclooxygenase-1 inhibitor SC-560 in the rat. J Pharm Pharm Sci. 2003 May-Aug;6(2):205-10.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
440.6±45.0 °C at 760 mmHg

[ Melting Point ]:
63 °C

[ Molecular Formula ]:
C₁₇H₁₂ClF₃N₂O

[ Molecular Weight ]:
352.738

[ Flash Point ]:
220.3±28.7 °C

[ Exact Mass ]:
352.059021

[ PSA ]:
27.05000

[ LogP ]:
6.13

[ Vapour Pressure ]:
0.0±1.0 mmHg at 25°C

[ Index of Refraction ]:
1.564

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi: Irritant;

[ Risk Phrases ]:
R36/37/38

[ Safety Phrases ]:
26-36

[ RIDADR ]:
NONH for all modes of transport

[ HS Code ]:
2933199090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933199090

[ Summary ]:
2933199090. other compounds containing an unfused pyrazole ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

Arachidonic acid downregulates acyl-CoA synthetase 4 expression by promoting its ubiquitination and proteasomal degradation.

J. Lipid Res. 55(8) , 1657-1667, (2014)

ACSL4 is a member of the long-chain acyl-CoA synthetase (ACSL) family with a marked preference for arachidonic acid (AA) as its substrate. Although an association between elevated levels of ACSL4 and ...

Mechanisms for proteinase-activated receptor 1-triggered prostaglandin E2 generation in mouse osteoblastic MC3T3-E1 cells.

Biol. Chem. 396(2) , 153-62, (2015)

We analyzed signaling mechanisms for prostaglandin E2 (PGE2) production following activation of proteinase-activated receptor-1 (PAR1), a thrombin receptor, in preosteoblastic MC3T3-E1 cells. PAR1 sti...

COX-2 inhibition improves retinal function in rats' ischemic eyes.

J. Ocul. Pharmacol. Ther. 30(8) , 634-41, (2014)

Retinal ischemia is a relatively simple model for studies in pharmacological neuroprotective intervention. The role of cyclooxygenase (COX) enzymes in ischemic insult has been variously shown to eithe...