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Description: LJI308 is a novel, potent, and pan-RSK (p90 ribosomal S6 kinase) inhibitor with potential antitumor activity. It inhibits RSK1, RSK2, and RSK3 with IC50s of 6 nM, 4 nM, and 13 nM, respectively. LJI308 is able to overcome chemoresistance by eliminating cancer stem cells. It 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.
Molecular Weight (MW)
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
Other info
Chemical Name: 2,6-Difluoro-4-[4-[4-(4-morpholinyl)phenyl]-3-pyridinyl]-phenol
InChi Key: YUYJEQHNWKQNBT-UHFFFAOYSA-N
InChi Code: InChI=1S/C21H18F2N2O2/c22-19-11-15(12-20(23)21(19)26)18-13-24-6-5-17(18)14-1-3-16(4-2-14)25-7-9-27-10-8-25/h1-6,11-13,26H,7-10H2
SMILES Code: OC1=C(F)C=C(C2=C(C3=CC=C(N4CCOCC4)C=C3)C=CN=C2)C=C1
Synonyms
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
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.
In Vivo
Animal model
Formulation & Dosage
References
Mol Cancer Res. 2014 May;12(5):803-12; Oncotarget. 2015 Aug 21;6(24):20570-7.
Purity ≥98%
COA
MSDS