HL-8 is a PI3Kα PROTAC degrader. HL-8 promotes the ubiquitination and degradation of PI3Kα. HL-8 reduces pAKT levels. HL-8 has anticancer activity against colon and cervical cancer (Pink: PI3Kα ligand; Blue: E3 ligase VHL ligand; Black: linker ) [1]. (Pink: PI3Kα ligand; Blue: VHL ligand; Black: linker ).
In Vitro, HL-8 (1 nM) inhibits PI3Kα kinase by 49.75%[1]. HL-8 (10 μM; 72 h) inhibits the proliferation of HT-29, HCT-116, and Hela cells by 72.18%, 50.30%, and 96.33%, respectively[1]. HL-8 (10 μM; 2-24 h) significantly degrades PI3Kα and reduces phosphorylated AKT levels in Hela cells[1].
References:
[1]. Wang H, et al. Design, synthesis and activity study of a novel PI3K degradation by hijacking VHL E3 ubiquitin ligase. Bioorg Med Chem. 2022 May 1;61:116707.
In Vitro, HL-8 (1 nM) inhibits PI3Kα kinase by 49.75%[1]. HL-8 (10 μM; 72 h) inhibits the proliferation of HT-29, HCT-116, and Hela cells by 72.18%, 50.30%, and 96.33%, respectively[1]. HL-8 (10 μM; 2-24 h) significantly degrades PI3Kα and reduces phosphorylated AKT levels in Hela cells[1].
References:
[1]. Wang H, et al. Design, synthesis and activity study of a novel PI3K degradation by hijacking VHL E3 ubiquitin ligase. Bioorg Med Chem. 2022 May 1;61:116707.