DBPR112 is an orally active furanopyrimidine-based EGFR inhibitor with IC50s of 15 nM for EGFRWT and 48 nM for EGFRL858R/T790M, capable of occupying the ATP-binding site and demonstrating significant antitumor efficacy.

EGFR (L858R/T790M):48 nM, EGFR (WT):15 nM

DBPR112 (0.32-1000 nM; 16 hours) induces reduction of phosphorylated EGFR in a dose-dependent manner[1]. DBPR112 shows the inhibitory activity against HCC827 (CC50=25 nM), H1975 (CC50=620 nM) and A431 Cell (CC50=1.02 μM) cell lines[1]. DBPR112 occupies the ATP-binding site and interacts with surrounding residues by covalent bonding, hydrogen bonds, and hydrophobic interactions, which give it a potent inhibitory activity against WT EGFR[1].

DBPR112 administered orally at 20-50 mg/kg for 5 days per week over 2 weeks significantly reduces tumor growth in the HCC827 tumor model. Oral administration of DBPR112 at 50 mg/kg once daily for 15 days results in a mean tumor growth inhibition of 34% in the H1975 tumor model [1]. Intravenous administration of DBPR112 at 5 mg/kg in rats shows a T1/2 of 2.3 hours, a CL of 55.6 mL/min•kg, and a Vss of 8.6 L/kg [1].