JBJ-02-112-05 is a potent, mutant-selective, allosteric and orally active inhibitor of EGFR with an IC 50 of 15 nM for EGFR L858R/T790M [1].

EGFR (L858R/T790M):15 nM

In Ba/F3 cells, JBJ-02-112-05 inhibits the activities of wildtype EGFR, EGFR L858R, EGFR L858R/T790M and EGFR L858R/T790M/C797S with IC 50 values of 9.29 μM; 8.35 μM; 8.53 μM and 2.13 μM, respectively [1]. JBJ-02-112-05 shows mutant selectivity through inhibiting mutant EGFR and downstream AKT and ERK1/2 phosphorylation in Ba/F3 cells stably transfected with EGFR L858R, EGFR L858R/T790M, EGFR L858R/T790M/C797S mutations [1].

Treatment with JBJ-02-112-05 (100 mg/kg; oral gavage; once daily; for 3 days; EGFR L858R/T790M/C797S genetically engineered mice) can inhibit phosphorylation of EGFR and downstream signaling pathways [1]. JBJ-02-112-05 exhibits a moderate half-life of 3 hours and a Cmax of 13.7 μM following 3 mg/kg intravenous (i.v.) dose. A 5 mg/kg oral dose of JBJ-02-112-05 achieves a half-life of 16.4 hours and a C Cmax of 1.31 μM [1]. Animal Model: EGFR L858R/T790M/C797S genetically engineered mice [1] Dosage: 100 mg/kg Administration: Oral gavage; once daily; for 3 days Result: Inhibited phosphorylation of EGFR and downstream signaling pathways.