pi3kδ in 8

PI3Kδ-IN-8 is a powerful and specific oral inhibitor of PI3Kδ, exhibiting an IC50 of 3.3 nM. It demonstrates preferential inhibition of PI3Kδ when compared to PI3Kα, PI3Kβ, and PI3Kγ, with IC50 values of 377.2 nM, 241.6 nM, and 17.9 nM, respectively. Furthermore, PI3Kδ-IN-8 possesses notable anti-tumor efficacy.

PROTACPI3Kδ degrader-1 is a covalent PI3Kδ-targeting PROTAC degrader that targets lysine, with a DC50 of 3.98 nM. It exhibits potent antiproliferative activity and selective PI3Kδ inhibition (IC50: 8 nM). Additionally, PROTACPI3Kδ degrader-1 effectively degrades p-AKT, induces cell cycle arrest in the G1 phase, and promotes apoptosis and autophagy. It also significantly suppresses tumor growth in the SU-DHL-6 xenograft mouse model.

PI3Kα-IN-21 (compound 8) is a selective inhibitor of PI3Kα, demonstrating greater selectivity over PI3Kβ, PI3Kγ, and PI3Kδ by factors of 10.41, 16.99, and 37.53 respectively (IC50: 96.89/568.24/397.48 nM). This compound inhibits cancer cell activity, proliferation, and migration while inducing mitochondrial apoptosis through the PI3K/Akt/mTOR pathway. Additionally, PI3Kα-IN-21 has shown in vivo antitumor efficacy in a mouse model of non-small cell lung cancer.