product name SC-514
Description: SC-514 is an orally active, selective and reversible, ATP-competitive IKK-2 inhibitor with IC50 of 3-12 μM, blocks NF-κB-dependent gene expression, it does not inhibit other IKK isoforms or other serine-threonine and tyrosine kinases. SC-514 a candidate compound targeting osteoclastogenesis. SC-514 dose-dependently inhibits RANKL-induced osteoclastogenesis with an IC50 of <5μM. At high concentrations, SC-514 (≥12.5μM) induced apoptosis and caspase 3 activation in RAW264.7 cells. Targeting IKKβ by SC-514 presents as a potential treatment for osteoclast-related disorders such as osteoporosis and cancer-induced bone loss.
References: J Biol Chem. 2003 Aug 29;278(35):32861-71.
224.3
Formula
C9H8N2OS2
CAS No.
354812-17-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 45 mg/mL (200.6 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
GK 01140
other peoduct :
| In Vitro |
In vitro activity: SC-514 inhibits the native IKK complex or recombinant human IKK-1/IKK-2 heterodimer and IKK-2 homodimer similarly. SC-514 inhibits transcription of NF-κB-dependent IL-6, IL-8, and COX-2 genes in IL-1β-induced rheumatoid arthritis-derived synovial fibroblasts (RASFs) with IC50s of 20, 20 and 8 μM. 100 μM SC-514 blocks the phosphorylation and degradation of IκBα and also reduces the level of translocation of p65 into the nucleus in IL-1β-treated RASFs SC-514 does not inhibit the phosphorylation and activation of the IKK complex. SC-514 induces a delay but not a complete blockade in IκBα phosphorylation and degradation. SC-514 treatment cells shows a slightly slowed, decreased import of p65 into the nucleus and a faster export of p65 from the nucleus. SC-514 inhibits the phosphorylation of either IκBα or p65 similarly. Kinase Assay: Cell Assay: SC-514 inhibits all forms of recombinant human IKK-2 with IC50 values in the 3–12μM range. It also inhibits the native IKK complex. SC-514 specifically binds at the ATP-binding site of IKK-2 and exerts a reversible and competitive inhibition with ATP. However, SC-514 shows non-competitive inhibition with the IκB site. As an inhibitor of IKK-2, SC-514 is found to block the phosphorylation and degradation of IκBα and reduce the translocation level of p65 into the nucleus in IL-1β-treated RASFs. Additionally, SC-514 shows dose-dependent inhibition in the transcription of NF-κB-induced genes, including IL-6, IL-8, and COX-2. Moreover, SC-514 shows efficacious in reduction of LPS-induced TNFα production in the acute model of inflammation. SC-514 is also reported to inhibit the osteoclastogenesis in BMM cells through attenuating RANKL-induced activation of NF-κB. |
|---|---|
| In Vivo | SC-514 is efficacious in an acute model of inflammation, namely LPS-induced serum TNF-α production. SC-514 (50 mg/kg, i.p.) inhibits TNF-αproduction in vivo by ~70%. |
| Animal model | |
| Formulation & Dosage | 50 mg/kg; i.p. injection |
| References | J Biol Chem. 2003 Aug 29;278(35):32861-71. |
