Gly-PEG3-BA is a PROTAC degrader that targets EML4-ALK. It effectively degrades the EML4-ALK protein in H3122 cells (EML4-ALK positive) with a DC50 of 0.50 μM. In H1975 cells (EGFRL858R/T790M double mutant), Gly-PEG3-BA significantly reduces the levels of the EGFR mutant (L858R/T790M) protein, with a DC50 of 20.15 μM. Additionally, Gly-PEG3-BA exhibits strong antiproliferative activity against H3122 cells and H1975 cells, with IC50 values of 0.84 μM and 20.74 μM, respectively. It is useful for research related to non-small cell lung cancer.

Gly-PEG3-BA (0-20 μM, 72 hours) demonstrates highly selective targeted activity against EGFR in H1975 cells carrying EGFR L858R/T790M double mutations, and induces dose-dependent targeted degradation of EML4-ALK fusion protein in H3122 (EML4-ALK fusion gene) cells. At concentrations of 0-20 μM for either 48 or 72 hours, Gly-PEG3-BA effectively downregulates EML4-ALK and EGFR mutant levels, exhibiting strong antiproliferative effects in H3122 (EML4-ALK) and H1975 (EGFR-L858R/T790M) cells, with IC50 values of 0.84 μM and 20.74 μM, respectively. The compound reduces EML4-ALK or mutant EGFR protein levels in a dose-dependent manner in H3122 and H1975 cells. Gly-PEG3-BA induces degradation of EML4-ALK and mutated EGFR, a process mediated by ZYG11B and ZER1, as confirmed by knockdowns of ZYG11B and ZER1 expression in H3122 and H1975 cells.