perk

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.

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

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

PERK-IN-3 is a potent inhibitor of PERK (IC50 of 7.4 nM).

(S)-PERK-IN-5, the S-enantiomer of PERK-IN-5, is a PERK inhibitor with an IC50 range of 0.101-0.250 μM.

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.

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

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

Piperkadsin A effectively inhibits reactive oxygen species (ROS) production, specifically targeting PMA-induced ROS in human polymorphonuclear neutrophils, exhibiting an inhibition concentration (IC50) of 4.3 μM [1].

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

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.

ONO-8130 is an orally available antagonist of EP1 receptor.

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.

GSK621 is a specific and potent AMPK activator.

K-Ras G12C-IN-4, is a potent Covalent Inhibitor of KRASG12C..

ML417 is a selective and brain-penetrant agonist of D3 dopamine (EC50: 38 nM).

IACS-13909 (BBP-398), a specific and potent allosteric inhibitor of SHP2, that suppresses signaling through the MAPK pathway.

G-573 is an allosteric inhibitor of MEK that is both potent and selective. The IC(50) value for pERK inhibition in HCT116 tumours by G-573 was estimated to be 0.406  µM. The IC(50) values for tumour growth inhibition in HCT116 and H2122 were estimated to be 3.43 and 2.56 µM, respectively. ED(50) estimates in HCT116 and H2122 mouse xenograft models were estimated to be ~4.6 and 1.9 mg/kg/day, respectively.

Angiogenesis inhibitor BT2 is a novel inhibitor of angiogenesis and vascular permeability, inhibiting ERK phosphorylation and the expression of FosB/ΔFosB, VCAM-1, and many genes involved in proliferation, migration, angiogenesis, and inflammation, interacting with MEK1, suppressing retinal CD31, pERK, VCAM-1, and VEGF-A165 expression.

KRAS G12D modulator-1 (compound 6), a potent modulator of KRAS G12D, exhibits IC50 values of 1-10 μM against NEA-G12D, PPI-G12D, and p ERK-AGS, and is utilized in cancer research [1].

PF-07284892 (ARRY-558) is an orally active, potent SHP2 inhibitor with an IC50 of 21 nM, known to reduce the expression of pERK [1] [2].

SOS1-IN-13 is a potent inhibitor of son of sevenless homolog 1 (SOS1), displaying IC50 values of 6.5 nM for SOS1 and 327 nM for pERK. SOS1-IN-13 holds significant research value in anticancer studies.

GSK143 dihydrochloride is a highly selective, orally active inhibitor of spleen tyrosine kinase (SYK), exhibiting a pIC 50 value of 7.5. It effectively inhibits phosphorylated Erk (pErk) with a pIC 50 value of 7.1. The compound demonstrates anti-inflammatory properties and hinders the recruitment of immune cells in the intestinal muscularis of mice.

SOS1-IN-12 is a potent inhibitor of SOS1, with a Ki of 0.11 nM, and exhibits an IC50 of 47 nM on pERK.

GSK143 is a potent orally active and highly selective inhibitor of spleen tyrosine kinase (SYK) with a pIC 50 of 7.5. Furthermore, GSK143 effectively inhibits phosphorylated Erk (pErk) with a pIC 50 value of 7.1. In addition, GSK143 exhibits promising anti-inflammatory properties by reducing inflammation and impeding the recruitment of immune cells in the intestinal muscularis of mice.

ML291 is a sufonamidebenzamide compound that induces the unfolded protein response (UPR) and overwhelms the adaptive capacity of UPR, resulting in apoptosis in various solid cancer models. It activates the PERK/eIF2a/CHOP apoptotic pathway of UPR and reduces leukemic cell burden [1].

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.

PLX7922, a RAF inhibitor, demonstrates binding affinity with BRAF V600E and exhibits inhibitory effects on pERK in BRAF V600E cell lines, while inducing pERK activation in mutant NRAS cell lines.

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)

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].

MSI-1701, an analogue of MSI-1436, enhances (MSI-1436) activity by increasing (pMEK) and (pERK) phosphorylation, thus promoting (PI3K AKT) pathway signaling and inhibiting apoptosis in neuronal cells, which may contribute to its neuroprotective effects.

HDAC-IN-50, a potent, orally active inhibitor targeting both FGFR (Fibroblast Growth Factor Receptor) and HDAC (Histone Deacetylase), exhibits IC50 values of 0.18, 1.2, 0.46, 1.4, 1.3, 1.6, 2.6, 13 nM for FGFR1, FGFR2, FGFR3, FGFR4, HDAC1, HDAC2, HDAC6, HDAC8, respectively. This dual inhibitor induces apoptosis and cell cycle arrest at the G0/G1 phase while decreasing the expression of phosphorylated FGFR1 (pFGFR1), phosphorylated ERK (pERK), and phosphorylated STAT3 (pSTAT3), thus demonstrating anti-tumor activity.

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

Avarol induces apoptosis in pancreatic ductal adenocarcinoma cells by activating PERK-eIF2α-CHOP signaling. Avarl also acts as a competitive AChE inhibitor which are non-hepatotoxic and neuroprotective agents for Alzheimer's disease.

SHP389 is an allosteric SHP2 inhibitor with an IC50 of 36 nM for both SHP2 and p-ERK.

RAS RAS-RAF-IN-1 is a potent inhibitor of RAS and RAS-RAF, exhibiting a KD of 5.0 μμ-15 μμ for cyclophilin A (CYPA) binding affinity and demonstrating antitumor activity[1].

1. Bufotalin (Bufotaline)e is a kind of poisonous secretions of toads.

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.

MEK-IN-5, a potent MEK inhibitor and nitric oxide (NO) donor, effectively decreases pMEK and pERK levels in a dose-dependent and time-dependent fashion. Additionally, it induces apoptosis in MDA-MB-231 cells.

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].