PERK

Zotatifin (eFT226) is a selective eIF4A inhibitor with antiviral and anticancer activities, blocking tumor growth driven by receptor tyrosine kinases and inhibiting Sox4 translation, inducing apoptosis.

Rocaglamide (Roc-A), isolated from the genus Aglaia, can be used to treat coughs, injuries, asthma, and inflammatory skin diseases. It is a potent inhibitor of NF-κB activation in T-cells.

GSK2606414 is a cell-permeable and orally active protein kinase R-like endoplasmic reticulum kinase(PERK)inhibitor with IC50 of 0.4 nM. GSK2606414 inhibits PERK activation in cells and suppresses the growth of human tumor xenografts in mice.

GCN2iB is an ATP-competitive inhibitor of serine/threonine protein kinase, stress-responsive kinase (GCN2), with IC50 of 2.4 nM.

SHP099 (SHP099 free base) free base is an effective, selective, orally bioavailable, and efficacious SHP2 inhibitor (IC50 =0.07 μM and p-ERK modulation in cells IC50 = 0.250 μM). SHP099 shows dose-dependent pathway inhibition and antitumor activity in xenograft models.

ATPγS tetralithium salt is a good substrate for RNA-stimulated nucleotide hydrolysis and RNA unwinding activity of eIF4A.

CCT020312 (0-9 µM, 24 h) treatment of medium HT29 cells for 24 h resulted in a concentration-dependent loss of P-S608-pRB signaling with linear response values between 1.8 and 6.1 µM.

ISRIB (trans-isomer) is a potent inhibitor of PERK (IC50=5 nM) that restores protein translation and prevents SG formation in the presence of P-eIF2α.

eIF4A3-IN-1 is a selective and potent inhibitor of eukaryotic initiation factor 4A3 (eIF4A3) with an IC50 value of 0.26 μM. eIF4A3-IN-1 inhibits cytosolic nonsense-mediated RNA decay at high concentrations.

BTdCPU is a potent activator of heme-regulated eIF2α kinase (HRI) . BTdCPU promotes eIF2α phosphorylation and induced apoptosis in resistant cell.

BTM-3528 is an activator of the mitochondrial protease OMA1 with anticancer activity.BTM-3528 activates the ISR via the mitochondrial protease OMA1, inducing OMA1-dependent cleavage of DELE1 and OPA1 and mitochondrial fragmentation.BTM-3528 induces cell growth arrest and apoptosis.

GCN2-IN-7 is an orally active, potent and selective inhibitor of the environmental sensing protein GCN2 with anti-tumor activity and can be used to study melanoma.

HC-5404 is a novel, potent and highly selective PERK (Protein kinase RNA-like Endoplasmic Reticulum Kinase) inhibitor, blocking the activation of the PERK pathway, which in turn inhibits the endoplasmic reticulum stress response signaling pathway, thereby exerting anti-tumor effects, and can be used to treat advanced solid tumors and renal cell Cancer.

DNL343 is a selective and potent eIF2B activator that crosses the blood-brain barrier and inhibits the assembly of stress granules (SGs) induced by the C9ORF72 dipeptide repeats. DNL343 may be useful in the study of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS).

2BAct is a novel eif2b activator, preventing neurological defects caused by a chronic integrated stress response

4EGI-1, a competitive eIF4E eIF4 g interaction inhibitor, binds to eIF4E(KD=25 μM).

GCN2-IN-1 (A-92) is an effective GCN2 inhibitor and can be utilized in cancer research as a chemotherapeutic agent.

ISRIB is a potent and selective PERK inhibitor.

GSK2656157 is a highly specific and ATP-competitive PERK inhibitor (IC50: 0.9 nM) in a cell-free assay. The selectivty is 500-fold higher against a panel of 300 kinases.

Salubrinal, a phosphatases (PP1) inhibitor(IC50=1.7 μM), exhibits function on the eukaryotic translation initiation factor 2 subunit (eIF2α).

Briciclib (ON 014185) is a small molecule that inhibits cyclin D1 accumulation in Y cells.

Takeda-6d, a novel, potent DFG-out RAF/vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor, inhibits B-RAF and VEGFR2 with IC50 of 7.0nM and 2.2nM.

BAY 2965501 is a potent and selective diacylglycerol kinase zeta (DGKζ) inhibitor that induces pERK activation, and it can be utilized in cancer research.

Vaccarin is a major flavonoid glycoside in Vaccariae semen, its biotransformation pathways involves methylation, hydroxylation, glycosylation and deglycosylation.