JCN037

Research use only, not for human use.

JCN037 is potent, non-covalent and brain-penetrant inhibitor of EGFR(EGFR, p-wtEGFR and pEGFRvⅢ with IC50 of 2.49 nM, 3.95 nM, 4.48 nM , respectively).

JCN037 is potent, non-covalent and brain-penetrant inhibitor of EGFR(EGFR, p-wtEGFR and pEGFRvⅢ with IC50 of 2.49 nM, 3.95 nM, 4.48 nM , respectively).Relative to the conventional EGFR TKIs erlotinib and lapatinib, JCN037 displayed potent activity against EGFR amplified/mutant patient-derived cell cultures, significant BBB penetration (2:1 brain-to-plasma ratio), and superior efficacy in an EGFR-driven orthotopic glioblastoma xenograft model.

Western Blot Analysis.Cell Line:GBM39 and GS025 cells.Concentration:0-3333 nM Incubation Time:Result:Downregulated pEGFRvⅢ, p Akt, p-ERK, and p-S6 protein levels, significantly.

JCN037 (compound 5) exhibits low oral bioavailability due to a rapid hydroxylation of the fused 1,4-dioxane ring, suggesting first pass metabolism.JCN037 (compound 5, 300 mg/kg, BID) treatment provides a significant survival benefit, whereby median survival increased by 47% from 37.5 days to 55 days with 5 treatment.

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Angiogenesis

EGFR

EGFR

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2305154-31-6

376.18

C16H11BrFN3O2

>98% (HPLC)

In Vitro:?DMSO : 250 mg/mL (664.58 mM)

Fc1c(Br)cccc1Nc1ncnc2cc3OCCOc3cc12

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(-20℃)

With Ice Pack

≥ 2 years