SIAIS164018 drochloride is a PROTAC-based ALK and EGFR degrader, with IC50 value of 2.5 nM and 6.6 nM for ALK and ALK G1202R, respectively. SIAIS164018 drochloride strongly inhibits cancer cells migration and invasion, causes G1 cell cycle arrest and induces apoptosis. SIAIS164018 drochloride exhibits better property than Brigatinib .
SIAIS164018 (0-1 μM; 16 h) drochloride significantly inhibits SR cell proliferation[1].SIAIS164018 (0-100 nM; 72 h) drochloride shows better cell proliferation inhibition than Brigatinib does in ALK (G1202R) over-expressing 293T and EGFR expressing H1975 cell lines[1].SIAIS164018 (100 nM; 24 or 48 h) drochloride induces a significant G1 cell cycle arrest in ALK-negative Calu-1 and MDA-MB-231 cells[1].SIAIS164018 (0.01-1000 nM; 16h) drochloride down-regulates the protein level of FAK, PYK2, FER, RSK1, and GAK in ALK-positive SR and ALK-negative Calu-1 cell lines[1].
References:
[1]. Ren C, et al. Discovery of a Brigatinib Degrader SIAIS164018 with Destroying Metastasis-Related Oncoproteins and a Reshuffling Kinome Profile. J Med Chem. 2021 Jul 8;64(13):9152-9165.