PROTAC EGFR degrader 5

PROTAC EGFR degrader 5 (Compound 10), a PROTAC EGFR degrader, potently degrades EGFRDel19 in HCC827 cells with the DC50 of 34.8 nM. PROTAC EGFR degrader 5 significantly induces the apoptosis of HCC827 cells and arrest the cells in G1 phase[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> EGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> EGFR

Signaling Pathways >> PROTAC >> PROTAC

EGFR:34.8 nM (DC50)

PROTAC EGFR degrader 5 (PROTAC 10, 0-10 μM approximately, 72 h) inhibits HCC827 cell (NSCLC cell) proliferation with an IC50 value of 0.22 μM[1]. PROTAC EGFR degrader 5 (1 nM-10 μM, 48 h or 4-96 h) concentration-dependently and time-dependently degrades EGFR with a DC50 value of 34.8 nM in HCC827 cells[1]. PROTAC EGFR degrader 5 (0.1-1 μM, 36 h) concentration-dependently inhibits EGFR and downstream Akt phosphorylation in HCC827 cells[1]. PROTAC EGFR degrader 5 (0.1-10 μM, 48 h) displays weak degradation activity on EGFR in H1975 and A549 cells[1]. PROTAC EGFR degrader 5 (0.1-1 μM, 32 h) dose-dependently induces the apoptosis of HCC827 cells and arrests the cells in G1 phase[1]. Cell Proliferation Assay[1] Cell Line: HCC827, H1975, A549, A431 Concentration: 0-10 μM approximately Incubation Time: 72 h Result: Displayed more potent anti-proliferative activity against HCC827 cells than other cells, IC50 values: 0.22 μM (HCC827), > 10μM (H1975, A549, A431), respectively. Western Blot Analysis[1] Cell Line: HCC827 cell Concentration: 1 nM-10 μM Incubation Time: 48h for concentration-dependent assay, 4-96 h for time-dependent assay Result: Degraded EGFR with a DC50 value of 34.8 nM in HCC827 cell in a dose-dependent manner. Apoptosis Analysis[1] Cell Line: HCC827 cell Concentration: 0.1 μM, 1 μM Incubation Time: 32 h Result: Induced cell apoptosis in a dose-dependent manner. Cell Cycle Analysis[1] Cell Line: HCC827 cell Concentration: 0.1 μM, 1 μM Incubation Time: 32 h Result: Induced cell cycle arrest in G1 phase.

[1]. Hao Zhang, et al. Discovery of potent epidermal growth factor receptor (EGFR) degraders by proteolysis targeting chimera (PROTAC). Eur J Med Chem. 2020 Mar 1;189:112061.