egfr (cell: hcc827)

MS 39 is a potent Proteolysis Targeting Chimera (PROTAC) designed to degrade the Epidermal Growth Factor Receptor (EGFR). The molecule is composed of three structural motifs: an EGFR target ligand (red part), a VHL E3 ligase ligand (S,R,S)-AHPC (blue part), and an undecanedioic acid linker (black part). By facilitating the formation of a ternary complex between EGFR and the VHL E3 ubiquitin ligase, MS 39 triggers the polyubiquitination and subsequent proteasomal degradation of the receptor. MS 39 effectively reduces EGFR protein levels and inhibits downstream oncogenic signaling in HCC-827 and H3255 cell lines, leading to significant suppression of H3255 cancer cell proliferation.

Erlotinib (NSC-718781) is an EGFR inhibitor (IC50: 2 nM). It is used for the treatment of non-small cell lung cancer.

EGFR-IN-151 (Compound 10) inhibits EGFR and its downstream signaling pathways ERK/STAT3. It effectively suppresses the proliferation of various lung cancer cells, with IC50 values of 11.7, 5.19, 7.32, and 1.53 μM for NCI-H1781, HCC827, NCI-H3255, and NCI-H1975, respectively. Additionally, EGFR-IN-151 hinders colony formation and cell migration in H1975, induces G1 phase cell cycle arrest, and triggers apoptosis in H1975 cells.

Olmutinib (HM61713, BI 1482694) is an orally available small molecule, a mutant-selective inhibitor of epidermal growth factor receptor (EGFR) with potential antineoplastic activity. Olmutinib binds to and inhibits mutant forms of EGFR, thereby leading to cell death of EGFR-expressing tumor cells. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced as compared to non-selective EGFR inhibitors which also inhibit the EGFR wild-type form.

PROTAC EGFR degrader 4 is a potent molecule designed to target and degrade mutant EGFR, effectively inducing degradation of EGFR del19 and EGFR L858R/T790M with DC50 values of 0.51 nM and 126 nM, respectively. It significantly inhibits the growth of HCC827 and H1975 cell lines, demonstrating IC50 values of 0.83 nM and 203.1 nM, respectively. The induced degradation of EGFR by this compound is associated with autophagy [1].

PROTAC EGFR Degrader 5 (Compound 10), a potent degrader of EGFR Del19 in HCC827 cells, achieves this with a DC50 of 34.8 nM. This compound effectively induces apoptosis in HCC827 cells and causes cell cycle arrest in the G1 phase [1].

PROTAC EGFR degrader 8 (T-184) is a PROTAC that selectively degrades the epidermal growth factor receptor (EGFR) with a DC50 of 15.56 nM in HCC827 cells, and inhibits the growth of cell lines H1975, PC-9, and HCC827 with IC50 values of 7.72 nM, 121.9 nM, and 14.21 nM, respectively. This compound is used primarily for cancer research, particularly in the context of non-small cell lung cancer (NSCLC) [1].