PERK

ATPγS tetralithium salt is a substrate for nucleotide hydrolysis and RNA unraveling activity of the eukaryotic translation initiation factor eIF4A, associated with p97 mutants and prions.

GSK2606414 is an oral-available and specific PERK inhibitor (IC50=0.4 nM).

CCT020312 is a selective activator of EIF2AK3 and PERK. CCT020312 durably inhibits cell proliferation and elicits the phosphorylation of EIF2A.

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).

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

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.

ISRIB is a potent and selective PERK inhibitor.

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.

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

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.

AMC-01 has potential antiviral activity and induces dose- and time-dependent inactivation of eIF2-α via phosphorylation of serine residue 51. AMC-01 can be used to study atherosclerosis and Parkinson's syndrome.

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.

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

Sal003, an effective cell-permeable analog, inhibitis the eIF2α phosphatase.

MK-28 is a selective PERK agonist that reduces toxicity and prolongs survival in a Huntington's disease model.MK-28 has a significant killing effect on MK28 gastric cancer cells.

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

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

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

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

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

AMG PERK 44 is an orally active and selective PERK inhibitor (IC50: 6 nM) that induces autophagy. It also inhibits GCN2 (IC50: 7300 nM) and B-Raf (IC50 >1000 nM), making it useful for cancer research.

PERK-IN-4 is a potent and selective PERK inhibitor with an IC50 value of 0.3 nM, used in the study of cancer and neurological disorders.

4E1RCat is a dual inhibitor of eIF4E:eIF4 g and eIF4E:4E-BP1 interaction. And it inhibits the binding of eIF4 g to eIF4E with IC50 of 3.2 μM.

MSU-42011 is an orally active retinoid X receptor-like (RXR) agonist. It potently inhibits the expression of iNOS, low SREBP-induced and activated RXR, and p-ERK at the protein level. MSU-42011 has demonstrated antitumor activity in a [kras]-driven mouse model of lung cancer and is effective for the treatment of preclinical [kras]-driven lung cancer with immunomodulatory activity.

PERK-IN-6 is a novel and highly potent PERK inhibitor (IC50:2.5 nM).

GP 1a is a potent agonist of cannabinoid receptor 2 (CB2) (EC50=7.1), as shown in cAMP, GTPγS and β-arrestin recruitment assays. GP 1a is approximately 30-fold more selective for CB2 receptors than CB1 receptors and increases P-ERK1/2 expression in HL-60 cells in vitro. GP 1a is beneficial for skin wound healing. GP 1a inhibits inflammation and fibrogenesis while promoting epithelial re-formation.

SBI-0640756 (SBI-756) (SBI-756) is a first-in-class inhibitor that targets eIF4G1 and disrupts the eIF4F complex.

4E2RCat is an inhibitor of eIF4E-eIF4G interaction (IC50 = 13.5 μM) and effectively blocks coronavirus replication, as evidenced by reduced viral protein expression and decreased production of infectious virus.

Azoramide, a small-molecule modulator, has the antidiabetic activity of unfolded protein response.

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.