LJI-308

• CAT Number: I002102
• CAS Number: 1627709-94-7
• Molecular Formula: C₂₁H₁₈F₂N₂O₂
• Molecular Weight: 368.38
• Purity: ≥95%
• Target: S6 Kinase
• Solubility: DMSO: ≥ 32 mg/mL
• Storage: Store at -20°C
• IC50: 6/4/13 nM
• IUPAC Name: 2,6-difluoro-4-[4-(4-morpholin-4-ylphenyl)pyridin-3-yl]phenol
• InChI: 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
• InChIKey: YUYJEQHNWKQNBT-UHFFFAOYSA-N
• SMILES: C1COCCN1C2=CC=C(C=C2)C3=C(C=NC=C3)C4=CC(=C(C(=C4)F)O)F

LJI308 is an effective pan-RSK inhibitor with IC50 values of 6nM, 4nM and 13nM for RSK1, RSK2 and RSK3, respectively. LChemicalbook JI308 inhibits phosphorylation of RSK ( T359 / S363 ) and YB-1 ( S102 ) in irradiated, EGF-treated and KRAS-expressing cells.

Reference

1:Oncotarget. 2015 Aug 21;6(24):20570-7. Inhibition of RSK with the novel small-molecule inhibitor LJI308 overcomes chemoresistance by eliminating cancer stem cells.Davies AH,Reipas K,Hu K,Berns R,Firmino N,Stratford AL,Dunn SE, PMID: 26011941 PMCID: PMC4653026 DOI: 10.18632/oncotarget.4135 Abstract: The triple-negative breast cancer (TNBC) subtype is enriched in cancer stem cells (CSCs) and clinically correlated with the highest rate of recurrence. Several studies implicate the RSK pathway as being pivotal for the growth and proliferation of CSCs, which are postulated to drive tumor relapse. We now address the potential for the newly developed RSK inhibitor LJI308 to target the CSC population and repress TNBC growth and dissemination. Overexpression of the Y-box binding protein-1 (YB-1) oncogene in human mammary epithelial cells (HMECs) drove TNBC tumor formation characterized by a multi-drug resistance phenotype, yet these cells were sensitive to LJI308 in addition to the classic RSK inhibitors BI-D1870 and luteolin. Notably, LJI308 specifically targeted transformed cells as it had little effect on the non-tumorigenic parental HMECs. Loss of cell growth, both in 2D and 3D culture, was attributed to LJI308-induced apoptosis. We discovered CD44+/CD49f+ TNBC cells to be less sensitive to chemotherapy compared to the isogenic CD44-/CD49f- cells. However, inhibition of RSK using LJI308, BI-D1870, or luteolin was sufficient to eradicate the CSC population. We conclude that targeting RSK using specific and potent inhibitors, such as LJI308, delivers the promise of inhibiting the growth of TNBC.