perk-in-2

PERK-IN-2 is a potent inhibitor of PERK with an IC50 of 0.2 nM.

GCN2-IN-6 is also a eIF2α kinase PERK inhibitor with an IC50 of 0.26 nM (in enzymatic assay) and 230 nM (in cells). GCN2-IN-6  is a potent, and orally available GCN2 inhibitor confirmed by in-house enzymatic (IC50 of 1.8 nM) and cellular assays (IC50 of 9

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 is a highly selective, potent, orally active inhibitor of protein kinase R-like endoplasmic reticulum (ER) kinase (PERK), displaying inhibition with IC50 values of 2 nM for PERK and 9 nM for p-eIF2α. PERK-IN-5 significantly inhibited tumor growth in the 786-O renal cell carcinoma xenograft tumor model.

PROTAC SOS1 degrader-2, a potent degrader of PROTAC SOS1, effectively reduces the expression of pERK and RAS-GTP in a dose-dependent manner. It significantly inhibits tumor growth in vivo [1].

Antiproliferative agent-23, a microtubule-destabilizing agent (MDA), disrupts the tubulin-microtubule system, leading to apoptosis through a mitochondrion-dependent pathway. This involves downregulation of Bcl-2 protein, upregulation of Bax and Cyt c proteins, and activation of the caspase cascade. Additionally, it induces reactive oxygen species (ROS)-mediated endoplasmic reticulum stress in A549 CDDP cells (cisplatin-resistant cancer cell line) through the PERK ATF4 CHOP signaling pathway, demonstrating anti-tumor activity [1].