perk in 2

PERK-IN-2 is a potent inhibitor of PERK(IC50 of 0.2 nM).

PERK eIF2α activator 1 (compound V8) 为一种具备抗肿瘤特性的黄酮类化合物，能够诱发细胞凋亡并激活PERK-eIF2α-ATF4通路。此外，该化合物还能抑制HepG2细胞的增殖，其IC50值为23 μM。

GCN2-IN-6 经酶法和细胞分析证实，是一种口服有效GCN2抑制剂，IC50分别为1.8 nM 和9.3 nM。GCN2-IN-6 还是 eIF2α 激酶PERK 抑制剂，在酶法测定和细胞测定中的IC50分别为 0.26 nM 和 230 nM。

8(E),10(E),12(Z)-Octadecatrienoic acid is a conjugated polyunsaturated fatty acid (PUFA) that has been found inC. officinalisseed oil and has anticancer activity.1,2,3It inhibits the growth of Caco-2 cells when used at concentrations ranging from 10 to 50 μM.28(E),10(E),12(Z)-Octadecatrienoic acid (10 μM) induces formation of thiobarbituric acid reactive substances (TBARS) and apoptosis in DLD-1 colorectal adenocarcinoma cells.3It also inhibits prostaglandin biosynthesis in sheep vesicular gland microsomes (IC50= 31 μM).4 1.Crombie, L., and Holloway, S.J.The biosynthesis of calendic acid, octadeca-(8E,10E, 12Z)-trienoic, acid, by developing marigold seeds: origins of (E,E,Z) and (Z,E,Z) conjugated triene acids in higher plantsJ. Chem. Soc. Perk. T. 12425-2434(1985) 2.Yasui, Y., Hosokawa, M., Kohno, H., et al.Growth inhibition and apoptosis induction by all-trans-conjugated linolenic acids on human colon cancer cellsAnticancer Res.26(3A)1855-1860(2006) 3.Shinohara, N., Ito, J., Tsuduki, T., et al.Jacaric acid, a linolenic acid isomer with a conjugated triene system, reduces stearoyl-CoA desaturase expression in liver of miceJ. Oleo Sci.61(8)433-441(2012) 4.Nugteren, D.H., and Christ-Hazelhof, E.Naturally occurring conjugated octadecatrienoic acids are strong inhibitors of prostaglandin biosynthesisProstaglandins33(3)403-417(1987)

PERK-IN-5 是一种高度选择性的、高效的、口服具有活力的蛋白激酶 R 样内质网 (ER) 激酶 (PERK) 抑制剂，能够作用于 PERK (IC50: 2 nM) 与 p-eIF2α (IC50: 9 nM)。在 786-O 肾细胞癌异种移植瘤模型中，PERK-IN-5 可以明显抑制肿瘤生长。

PROTACSOS1 degrader-2 是一种有效的 PROTACSOS1降解剂。PROTACSOS1 Degrader-2 以剂量依赖性方式降低 pERK 和 RAS-GTP 的表达水平。PROTACSOS1degrader-2 在体内显著抑制肿瘤生长。

Antiproliferative agent-23，一种微管去稳定剂(MDA)，通过扰乱微管蛋白-微管系统来发挥作用。该化合物通过降低Bcl-2蛋白水平、提高Bax和Cyt c蛋白水平以及激活半胱天冬酶级联反应和线粒体依赖途径来诱导细胞凋亡。此外，Antiproliferative agent-23还能在A549 CDDP细胞（顺铂耐药癌细胞系）中通过PERK ATF4 CHOP信号通路激活ROS介导的内质网应激，展现出抗肿瘤活性。