PERK

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.

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.

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

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).

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.

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.

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

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.

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

ISRIB is a potent and selective PERK inhibitor.

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

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

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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

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

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.

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.

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

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

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.

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.

SHP389 is a highly effective allosteric inhibitor of SHP2, inhibiting SHP2 and p-ERK, used in cancer research.

HC-7366 (GCN2 modulator-1) is an orally active GCN2 kinase activator with antitumor activity, inducing tumor growth inhibition.

HC-5404-Fu is an inhibitor of PERK with anti-tumor activity. This compound inhibits the signaling pathway of the endoplasmic reticulum stress response. Additionally, HC-5404-Fu increases the sensitivity of renal cell carcinoma cells to vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (TKIs). It holds potential for research into renal cell carcinoma, stomach cancer, metastatic breast cancer, small cell lung cancer, and other solid tumors.