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

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.