| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
SC-560 is a novel, potent,orally bioavailable and selective COX-1 (cyclooxygenase-1) inhibitor with an IC50 of 9 nM. SC-560 inhibited colony formation in soft agar and induced apoptosis in HCC cells in a dose-dependent manner. Moreover, SC-560 decreased the levels of the anti-apoptotic proteins survivin and XIAP and activated caspase-3 and -7 in a dose- and time-dependent fashion. SC-560 exhibits anti-tumor and apoptotic effects in human HCC cells. SC-560 extensively distributes into rat tissues, and has a CL approaching hepatic plasma flow. The drug displays low<15% and formulation dependent bioavailability after oral administration and demonstrates kidney toxicity.
| Targets |
COX-1 (IC50 = 9 nM); COX-2 (IC50 = 6.3 μM)
|
|---|---|
| ln Vitro |
In a concentration-dependent manner, the pre-dilution of COX-1 and SC-560 prevents arachidonic acid from being converted to PGE2. Compared to COX-1, SC-560 has an IC50 of 6.3 μM against COX-2, which is about 1,000 times greater[1]. SC-560 shows dose- and time-dependent suppression of the development of HCC cells. In soft agar, SC-560 also prevents colony formation and stimulates dose-dependent HCC cell proliferation. Furthermore, in a manner that is dependent on both dose and time, SC-560 activates caspases 3 and 7 and decreases the amounts of the anti-tumor cell growth sudan proteins Svivin and XIAP [2].
|
| ln Vivo |
Ionophore-stimulated TxB2 production was totally suppressed by injury of 10 or 30 mg/kg SC-560 1 hour prior to test, suggesting that SC-560 has biolesion availability and inhibits COX-1 in vivo [1]. In the scaffold tissue, SC-560 was extensively dispersed, and CL was in close proximity to the hepatic venous flow. The medication shows nephrotoxicity, limited bioavailability, and formulation dependence of less than 15% following epidermal formulation [3].
After an iv dose (10 mg/kg) of SC-560, serum AUC, t(1/2), CL and Vd were 9704 +/- 4038 ng h/mL, 5.4 +/- 0.8 h, 1.15 +/- 0.46 L/h/kg and 9.1 +/- 4.6 L/kg (mean +/- SD, n = 5), respectively. Oral administration of 10 mg/kg SC-560-PEG and MC (n=5 rats) yielded serum AUC, C max, t (max )and t (1/2) of 1203.4 +/- 130.3 and 523 +/- 208 ng h/mL, 218.5 +/- 86.9 and 119.8 +/- 15.5 ng/mL, 1.00 +/- 1.8 and 2.0+/- 0 h, 3.7 +/- 1.6 and 2.7 +/- 1.7 h (mean +/- SD, n = 5), respectively. A single oral dose 10 mg/kg of SC-560 in PEG resulted in an increase in NAG excretion in urine and a reduction in 0-24 h urinary sodium, potassium, and chloride excretion. Conclusions: SC-560 extensively distributes into rat tissues, and has a CL approaching hepatic plasma flow. The drug displays low <15% and formulation dependent bioavailability after oral administration and demonstrates kidney toxicity.[3] |
| Enzyme Assay |
The enzymes cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) catalyze the conversion of arachidonic acid to prostaglandin (PG) H2, the precursor of PGs and thromboxane. These lipid mediators play important roles in inflammation and pain and in normal physiological functions. While there are abundant data indicating that the inducible isoform, COX-2, is important in inflammation and pain, the constitutively expressed isoform, COX-1, has also been suggested to play a role in inflammatory processes. To address the latter question pharmacologically, we used a highly selective COX-1 inhibitor, SC-560 (COX-1 IC50 = 0.009 microM; COX-2 IC50 = 6.3 microM). SC-560 inhibited COX-1-derived platelet thromboxane B2, gastric PGE2, and dermal PGE2 production, indicating that it was orally active, but did not inhibit COX-2-derived PGs in the lipopolysaccharide-induced rat air pouch. Therapeutic or prophylactic administration of SC-560 in the rat carrageenan footpad model did not affect acute inflammation or hyperalgesia at doses that markedly inhibited in vivo COX-1 activity. By contrast, celecoxib, a selective COX-2 inhibitor, was anti-inflammatory and analgesic in this model. Paradoxically, both SC-560 and celecoxib reduced paw PGs to equivalent levels. Increased levels of PGs were found in the cerebrospinal fluid after carrageenan injection and were markedly reduced by celecoxib, but were not affected by SC-560. These results suggest that, in addition to the role of peripherally produced PGs, there is a critical, centrally mediated neurological component to inflammatory pain that is mediated at least in part by COX-2[1].
|
| Cell Assay |
In this study we investigated the expression of COX-1 in non-tumor and malignant human liver tissues, as well as the effects of the highly selective COX-1 inhibitor SC-560 on cell growth and apoptosis in human HCC cell lines. Expression of COX-1 was detected in nearly all the samples assayed, although with a high variability between non-tumoral (NT) and malignant tissues. The percentage of COX-1 positive cells was significantly higher in the NT tissues than in the tumors (p<0.0001). In well-differentiated HCC COX-1 expression was significantly higher than in the poorly-differentiated tissues (p<0.05). SC-560 showed a dose- and time-dependent inhibitory effect on HCC cell growth. The combination of the COX-1 inhibitor with nimesulide and CAY10404, two selective COX-2 inhibitors, resulted in additive effects on cell growth inhibition. SC-560 also inhibited colony formation in soft agar and induced apoptosis in HCC cells in a dose-dependent manner. Moreover, SC-560 decreased the levels of the anti-apoptotic proteins survivin and XIAP and activated caspase-3 and -7 in a dose- and time-dependent fashion. In conclusion, we report for the first time that the selective COX-1 inhibitor SC-560 exhibits anti-tumor and apoptotic effects in human HCC cells. Overall, our previous and present results suggest that both COX-1 and COX-2 inhibitors may have potential therapeutic implications in HCC patients[1].
|
| Animal Protocol |
The pharmacokinetics of SC-560 was studied in Sprague-Dawley rats (n = 5 per group) 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 were collected via a catheter inserted in the right jugular vein and serum samples were analysed for SC-560 using reverse phase HPLC. After oral administration of SC-560 in PEG, urine was also collected for 24 h and analysed for urinary sodium, chloride, and potassium as well as NAG.[3]
|
| References |
|
| Additional Infomation |
SC560 is a member of the class of pyrazoles that is 1H-pyrazole which is substituted at positions 1, 3 and 5 by 4-methoxyphenyl, trifluoromethyl and 4-chlorophenyl groups, respectively. Unlike many members of the diaryl heterocycle class of cyclooxygenase (COX) inhibitors, SC-560 is selective for COX-1. It has a role as a cyclooxygenase 1 inhibitor, a non-steroidal anti-inflammatory drug, an apoptosis inducer, an antineoplastic agent and an angiogenesis modulating agent. It is a member of pyrazoles, an organofluorine compound, an aromatic ether and a member of monochlorobenzenes.
5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole has been reported in Alstonia yunnanensis with data available. |
| Molecular Formula |
C17H12CLF3N2O
|
|---|---|
| Molecular Weight |
352.7382
|
| Exact Mass |
352.059
|
| Elemental Analysis |
C, 57.89; H, 3.43; Cl, 10.05; F, 16.16; N, 7.94; O, 4.54
|
| CAS # |
188817-13-2
|
| PubChem CID |
4306515
|
| Appearance |
White to yellow solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
440.6±45.0 °C at 760 mmHg
|
| Melting Point |
63 °C
|
| Flash Point |
220.3±28.7 °C
|
| Vapour Pressure |
0.0±1.0 mmHg at 25°C
|
| Index of Refraction |
1.564
|
| LogP |
6.13
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
24
|
| Complexity |
407
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC1C([H])=C([H])C(=C([H])C=1[H])C1=C([H])C(C(F)(F)F)=NN1C1C([H])=C([H])C(=C([H])C=1[H])OC([H])([H])[H]
|
| InChi Key |
PQUGCKBLVKJMNT-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C17H12ClF3N2O/c1-24-14-8-6-13(7-9-14)23-15(10-16(22-23)17(19,20)21)11-2-4-12(18)5-3-11/h2-10H,1H3
|
| Chemical Name |
5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole
|
| Synonyms |
SC-560; SC 560; SC-560; 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole; SC 560; 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)pyrazole; SC560; 5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole; 1H-Pyrazole, 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-; SC560.
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~283.49 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (8.50 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8349 mL | 14.1747 mL | 28.3495 mL | |
| 5 mM | 0.5670 mL | 2.8349 mL | 5.6699 mL | |
| 10 mM | 0.2835 mL | 1.4175 mL | 2.8349 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA