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，因此成为有希望的抗癌靶标。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），这是一种选择性PI3Kα抑制剂（IC ₅₀  = 5.9 nM，β/α，δ /α，γ/α= 101-，13-，38-倍。Western印迹分析证实了化合物37可以抑制人癌细胞中AKT的磷酸化，从而调节细胞PI3K / AKT / mTOR途径。并在体内进行进一步评估 针对SKOV-3异种移植物模型的研究表明，获得了剂量依赖性的抗肿瘤功效。