In various human cancers, PI3Ks pathway is ubiquitously dysregulated and thus become a promising anti-cancer target. To discover new potent and selective PI3K inhibitors as potential anticancer drugs, new pyrrolo[2,1-f][1,2,4]triazines were designed, leading to the discovery of compound 37 (CYH33), a selective PI3Kα inhibitor (IC₅₀ = 5.9 nM, β/α, δ/α,γ/α = 101-, 13-, 38-fold). Western blot analysis confirmed that compound 37 could inhibit phosphorylation of AKT in human cancer cells to modulate the cellular PI3K/AKT/mTOR pathway. And further evaluation in vivo against SKOV-3 xenograft models demonstrated that a dose-dependent antitumor efficacy was achieved.

在各种人类癌症中，PI3Ks 通路普遍失调，因此成为有前景的抗癌靶点。为了发现新的有效和选择性 PI3K 抑制剂作为潜在的抗癌药物，设计了新的吡咯并[2,1- f ][1,2,4]三嗪，从而发现了化合物37 ( CYH33 )，一种选择性 PI3Kα 抑制剂 (IC ₅₀ = 5.9 nM，β/α、 δ /α、γ/α = 101、13、38 倍）。 Western blot 分析证实，化合物37可以抑制人癌细胞中 AKT 的磷酸化，从而调节细胞 PI3K/AKT/mTOR 通路。针对 SKOV-3 异种移植模型的进一步体内评估表明，实现了剂量依赖性抗肿瘤功效。