| Description |
JBJ-04-125-02 is a potent, mutant-selective, allosteric and orally active EGFR inhibitor with an IC50 of 0.26 nM for EGFRL858R/T790M. JBJ-04-125-02 can inhibit cancer cell proliferation and EGFRL858R/T790M/C797S signaling. JBJ-04-125-02 has anti-tumor activities[1].
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| Related Catalog |
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| Target |
EGFR (L858R/T790M):0.26 nM (IC50)
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| In Vitro |
JBJ-04-125-02 (0-1000 nM; 72 hours; H1975 cells) treatment could inhibit cell proliferation of H1975 cells at low nanomolar concentrations[1]. JBJ-04-125-02 treatment also inhibits cell proliferation in Ba/F3 cells stably transfected with EGFRL858R, EGFRL858R/T790M, or EGFRL858R/T790M/C797S mutations[1]. The ability of JBJ-04-125-02 (0.01-10 μM) to inhibit EGFR phosphorylation using Ba/F3, H1975 and NIH-3T3 cells is examined. JBJ-04-125-02 demonstrates mutant selectivity by inhibiting mutant EGFR and downstream AKT and ERK1/2 phosphorylation[1]. Cell Proliferation Assay[1] Cell Line: H1975 cells Concentration: 0 nM, 0.1 nM, 1 nM, 10 nM, 100 nM, 1000 nM Incubation Time: 72 hours Result: Inhibited cell proliferation of H1975 cells at low nanomolar concentrations.
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| In Vivo |
JBJ-04-125-02 (50 mg/kg; oral gavage; once daily; for 15 weeks; EGFRL858R/T790M/C797S genetically engineered mice) treatment leads to marked tumor regressions within 4 weeks of treatment[1]. JBJ-04-125-02 exhibits a moderate half-life of 3 hours and a high area under curve of 728,577 min•ng/mL (AUClast) following 3 mg/kg intravenous (i.v.) dose. A 20 mg/kg oral dose of JBJ-04-125-02 achieves an average maximal plasma concentration of 1.1 μmol/L with an oral bioavailability of 3%[1]. Animal Model: EGFRL858R/T790M/C797S genetically engineered mice (GEM)[1] Dosage: 50 mg/kg Administration: Oral gavage; once daily; for 15 weeks Result: Led to marked tumor regressions within 4 weeks of treatment.
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| References |
[1]. To C, et al. Single and Dual Targeting of Mutant EGFR with an Allosteric Inhibitor. Cancer Discov. 2019 Jul;9(7):926-943.
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