9H-Purine-2,8-diamine, 9-[(3R)-1-(cyclopropylsulfonyl)-3-pyrrolidinyl]-N2-[4-(4-methyl-1-piperazinyl)phenyl]-N8-phenyl-

Biological Activity

EGFR-IN-11 is a fourth-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) with an IC50 of 18 nM for triple mutant EGFRL858R/T790M/C797S. EGFR-IN-11 significantly suppresses the EGFR phosphorylation, induce the apoptosis, and arrest cell cycle at G0/G1[1]. EGFR-IN-11 (Compound D9; 0.0001-10 μM; 72 hours) shows significantly potent anti-proliferation against HCC827 and H1975 cell lines with IC50s of 0.88 nM and 0.20 μM, respectively[1]. EGFR-IN-11 (0.01-1.00 μM for HCC827 cells; 0.1-10.00 μM for H1975 and A549 cells; 8 hours) suppresses EGFR phosphorylation in a concentration-dependent manner in the HCC827, H1975 and A549 cell line[1]. EGFR-IN-11 (1 μM; 24 h) potently induces the apoptosis of HCC827 cells.[1]EGFR-IN-11 (1 μM; 24 h) induces cell cycle arrests in HCC827 cell[1].

References

[1]. Lei H, et al. Discovery of novel 9-heterocyclyl substituted 9H-purines as L858R/T790M/C797S mutant EGFR tyrosine kinase inhibitors. Eur J Med Chem. 2019 Nov 16:111888.