(Rac)-JBJ-04-125-02 (JBJ-04-125-02 racemate) is a mutant-selective allosteric inhibitor of Epidermal growth factor receptor (EGFR) with potential anticancer activity.
JBJ-04-125-02 can inhibit cell proliferation in vitro. Osimertinib, an ATP-competitive covalent EGFR inhibitor, uniquely and significantly enhances the binding of JBJ-04-125-02 for mutant EGFR. The combination of osimertinib and JBJ-04-125-02 results in an increase in apoptosis, a more effective inhibition of cellular growth in vitro compared to either single agent alone.[1]
JBJ-04-125-02 can inhibit EGFR L858R/T790M/C797S signaling in vivo. The combination of osimertinib and JBJ-04-125-02 results in an increase in apoptosis, and an increased efficacy in vivo compared to either single agent alone.[1]
[1] Ciric To, et al. Cancer Discov. 2019 Jul;9(7):926-943.