product name PS-1145
Description: PS-1145 is a potent and specific IKK inhibitor with IC50 of 88 NM. PS1145 efficiently inhibited both basal and induced NF-kappaB activity in PC cells. PS1145 induced caspase 3/7-dependent apoptosis in PC cells and significantly sensitized PC cells to apoptosis induced by tumor necrosis factor alpha. PS1145 inhibited PC cell proliferation. PS1145 enhances apoptosis in DMBA-induced tumor in male Wistar rats. PS1145 can overcome imatinib resistance.
References: J Biol Chem. 2002 May 10;277(19):16639-47.
322.75
Formula
C17H11ClN4O
CAS No.
431898-65-6
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 64 mg/mL (198.3 mM)
Water: <1 mg/mL
Ethanol: 2 mg/mL warmed (6.2 mM)
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: PS-1145 blocks TNFalpha-induced NF-kappaB activation through inhibition of IkappaBalpha phosphorylation, and blocks the protective effect of IL-6 against Dex-induced apotosis. PS-1145 also inhibits paracrine MM cell growth and IL-6 secretion in BMSCs triggered by MM cell adherence. In human primary CD4(+) T cells, PS-1145 abrogates cell proliferation and impairs the activation of NF-κB and AP-1 transcription factors by engagement of CD3 and CD28 coreceptor Kinase Assay: PS-1145 are dissolved in DMSO and stored at −20 °C until use. Ki value of PS-1145 against the IKK complex is determined by measuring Km , ATP against varying fixed concentration of the inhibitor. Briefly, partially purified IKK complex obtained from unstimulated HeLa S3 cells are pre-activated using the catalytic domain of MEKK1 expressed in sf9. Kinase activity is assessed using a biotinylated IκBα peptide (250 μM, RHDSGLDSMKD,Km ,peptide = 30 μM,K m , ATP = 10 μM) and phospho-[Ser32]-phosphoantibodies in an ELISA format with appropriate standard curve for quantification. For PS-1145 Ki measurement, the activated IKK complex is first preincubated in varying fixed concentration of the inhibitor (0.1–1 μM) at 25 °C for 1 h. Then apparentK m measurement for MgATP is performed at each discrete inhibitor concentration. Cell Assay: The inhibitory effect of PS-1145 on MM growth is assessed by measuring MTT dye absorbance of the cells. Cells (MM.1S, U266, and RPMI8226 cell lines) from 48-h cultures are pulsed with 10 μL of 5 mg/ml MTT to each well for the last 4 h of 48-h cultures, followed by 100 μl of isopropanol containing 0.04N HCl. Absorbance is measured at 570 nm using a spectrophotometer. |
|---|---|
| In Vivo | In male Wistar rats with DMBA-induced skin tumor, PS-1145 (50 mg/kg, i.v.) enhances tumor cell apoptosis by up-regulating p53, activating caspases and down regulating NF-κB and VEGF factor, and thus induces the tumor progression. |
| Animal model | Male Wistar rats with DMBA-induced skin tumor |
| Formulation & Dosage | Dissolved in 0.4 mg/mL in DMSO and diluted with 0.9% NaCl; 50 mg/kg; i.v. injection |
| References | J Biol Chem. 2002 May 10;277(19):16639-47; J Immunol. 2012 Mar 15;188(6):2545-55; Cell Biol Int. 2015 Nov;39(11):1317-28. |
