product name LJI308
Description: LJI308 is a potent, and pan-RSK (p90 ribosomal S6 kinase) inhibitor with IC50 of 6 nM, 4 nM, and 13 nM for RSK1, RSK2, and RSK3, respectively. LJI308 overcomes chemoresistance by eliminating cancer stem cells. LJI308 targets the CSC population and repress TNBC growth and dissemination. LJI308 specifically targeted transformed cells as it had little effect on the non-tumorigenic parental HMECs. Targeting RSK using specific and potent inhibitors, such as LJI308, delivers the promise of inhibiting the growth of TNBC.
References: Mol Cancer Res. 2014 May;12(5):803-12; Oncotarget. 2015 Aug 21;6(24):20570-7.
368.38
Formula
C21H18F2N2O2
CAS No.
1627709-94-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 73 mg/mL (198.16 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: In MDA-MB-231 and H358 cells, LJI308 blocks cellular inhibition of RSK and its phosphorylation of YB1 on Ser102 with EC50 of 0.2–0.3 μM, and thus inhibits cell growth. In TNBC HTRY-LT cells, LJI308 also suppresses cell growth correlative with YB-1 inhibition Kinase Assay: Enzymatic activity of RSK isoforms 1, 2, and 3 is assessed using recombinant full-length RSK protein. RSK1 (1 nM), RSK2 (0.1 nM), or RSK3 (1 nM) is allowed to phosphorylate 200 nM peptide substrate (biotin-AGAGRSRHSSYPAGT-OH) in the presence of ATP at concentration equal to the Km for ATP for each enzyme (RSK1- 5 μM, RSK2- 20 μM, RSK3- 10 μM) and appropriate dilutions of RSK inhibitors in 50 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.1% BSA Fraction V, 0.01% Tween-20. After 150 min at room temperature, the reaction is stopped with 60 mM EDTA and extent of peptide phosphorylation was determined using an anti-phospho-AKT substrate antibody and AlphaScreen reagents as described by the manufacturer. Cell Assay: Cell growth under attached conditions is assessed by plating 1000 cells (MDA-MB-231 and H358 cells) per well on 96-well tissue culture-treated plates in cell growth medium. Appropriate dilutions of compound are 4 added medium above cells and cell growth was assessed after 72 hrs by addition of CellTiter Glo reagent according to manufacturer’s directions. |
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| References | Mol Cancer Res. 2014 May;12(5):803-12; Oncotarget. 2015 Aug 21;6(24):20570-7. |
