pi3kα-in-4

PI3Kα-IN-4 is a potent, selective and orally active inhibitor of PI3Kα, with an IC50 of 1.8 nM. PI3Kα-IN-4 has antitumor activity[1]. PI3Kα-IN-4 (compound 10) inhibits PI3Kα, β, δ, and γ, with IC50s of 1.8, 271.0, 13.9, and 13.8 nM, respectively in kinase assays[1].PI3Kα-IN-4 inhibits PI3Kα, β, δ, and γ, with IC50s of 12.1,1393, 183, and >10000 nM, respectively in cell based assays[1]. PI3Kα-IN-4 (compound 10) (30 mg kg; p.o. once daily for 21 d) achieves the best efficacy, which could inhibit tumor growth by 73.0% in mice[1].PI3Kα-IN-4 (15-40 mg kg; p.o. once daily for 30 d) dose dependently suppresses tumor growth by 62.5% (15 mg kg), 86.0% (30 mg kg) and 90.7% (40 mg kg), respectively in mice[1].PI3Kα-IN-4 (15-40 mg kg; p.o. once daily; 1-4 h) inhibits the phosphorylation of Akt in a dose- and time-dependent manner in vivo[1].PI3Kα-IN-4 shows high Cmax (mouse 22167, rat 2327 nM) and good bioavailability (mouse 59.4%, rat 46.9%) following oral administration (mouse 10, rat 3 mg kg)[1].PI3Kα-IN-4 shows t1 2 (mouse 0.99, rat 1.22 h) and low plasma clearance (mouse 4.16, rat 5.28 mL min kg) following intravenous injection (mouse 1, rat 1 mg kg)[1]. [1]. Dong J, et, al. Discovery of 3-Quinazolin-4(3 H)-on-3-yl-2, N-dimethylpropanamides as Orally Active and Selective PI3Kα Inhibitors. ACS Med Chem Lett. 2020 Jun 10; 11(7): 1463-1469.

(S)-PI3Kα-IN-4 is a potent inhibitor of PI3Kα, with an IC50 of 2.3 nM. (S)-PI3Kα-IN-4 shows 38.3-, 4.25-, and 4.93-fold selectivity for PI3Kα over PI3Kβ, PI3Kδ, and PI3Kγ, respectively. (S)-PI3Kα-IN-4 can be used for the research of cancer[1]. (S)-PI3Kα-IN-4 (compound 11) is a quinazolin-4(3H)-one derivative with 2-substituted-N-methylpropanamide substitution[1]. [1]. Dong J, et, al. Discovery of 3-Quinazolin-4(3 H)-on-3-yl-2, N-dimethylpropanamides as Orally Active and Selective PI3Kα Inhibitors. ACS Med Chem Lett. 2020 Jun 10;11(7):1463-1469.

PI3K-IN-46 是 PI3Kγ的特异性抑制剂。

PI3K-IN-47 (Compound 27) 是一款高度选择性的二价PI3K抑制剂，对PI3Kα具有极低的半抑制浓度（IC50: 0.44 nM）, 同时对PI3Kβ、PI3Kγ、PI3Kδ也表现出良好的抑制活性（IC50分别为7.18 nM、13.92 nM、22.83 nM）。此化合物能够有效诱导细胞周期在G1期发生暂停，并且在体外抑制集落形成和细胞迁移。对于HGC-27异种移植的小鼠模型，PI3K-IN-47能够显著抑制肿瘤生长。

PI3K-IN-41（compound 2）是一种具抗癌特性的光笼PI3K抑制剂（IC50=18.92 nM），适用于精确控制的癌症治疗。在紫外线照射下，PI3K-IN-41能有效抑制PI3K活性，并增强其抗癌效果。

PI3K-IN-48，PI3K抑制剂，对A549细胞系表现出1.55 ± 0.18 μM的IC50值。该化合物能够诱导G0 G1期细胞周期阻滞与细胞凋亡，并可下调p-PI3K与p-Akt的表达水平，适用于人类肺癌研究。

PI3K-IN-49 (compound 29)是一种有效的PI3K抑制剂，对 Avg T-47D 和 Avg SKBR3 细胞表现出抗增殖活性（WO2023239710A1; example 29）。

PI4KIIIbeta-IN-10 是PI4KIIIβ抑制剂，IC50=3.6 nM。

PI4KIIIbeta-IN-9 是一种 PI4KIIIβ抑制剂，其 IC50=7 nM。它也抑制 PI3Kδ (IC50:125 nM) 和 PI3Kγ (IC50:1046 nM)。

AMG 511 是一种高效的、口服有效的 I 类 pan-PI3K 抑制剂，对 PI3Kα, β, δ 和 γ 作用的 Ki 值分别为 4 nM, 6 nM, 2 nM 和 1 nM。它它显著抑制了 PI3K 信号，减少 p-Akt (Ser473)。它在小鼠胶质母细胞瘤移植瘤模型中具有抗肿瘤作用。

Bimiralisib (PI3K-IN-2) 是一种有效的，可渗透脑的 mTOR PI3K 抑制剂，是一种 mTORC1和 mTORC2抑制剂。它能够抑制 PI3Kα,PI3Kδ,PI3Kβ,PI3Kγ和 mTOR，IC50分别为 33 nM，451 nM，661 nM，708 nM 和 89 nM。

Onatasertib (CC223) 是一种口服有效的mTOR 激酶抑制剂，抑制mTOR 激酶，IC50为 16 nM。它抑制mTORC1和mTORC2。

PI3Kα-IN-17 (example 4) 作为一种PI3Kα 的高效抑制剂。