2. Signaling Pathways
  3. Cell Cycle/DNA Damage
  4. PERK

PERK

Protein kinase R-like endoplasmic reticulum kinase; PKR-like endoplasmic reticulum kinase

PERK

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Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is one of four known kinases that respond to cellular stress by deactivating the eukaryotic initiation factor 2 α (eIF2α) or other signal transduction cascades. PERK is highly expressed in pancreatic beta-cells and is essential in the beta-cell's development, differentiation and function.

PERK is a type I ER membrane protein containing a stress-sensing domain facing the ER lumen, a transmembrane segment, and a cytosolic kinase domain. Increase in unfolded proteins in the ER causes release of ER chaperones from the stress-sensing domain of PERK, which results in its activation via oligomerization and autophosphorylation at multiple serine, threonine, and tyrosine residues. Upon activation, PERK phosphorylates eIF2α at serine 51, rendering it an inhibitor of the ribosome translation initiation complex, consequently reducing overall protein synthesis. The reduction in translation reduces the ER burden, providing time for the cell to process or degrade the accumulated unfolded proteins to restore ER homeostasis. Although global protein synthesis is decreased, there is specific increased translation of certain mRNAs, such as ATF4, which modulate cellular survival pathways and enhance UPR function. Interfering with PERK function in cancer cells may limit their ability to thrive under hypoxia or nutrient deprived conditions and lead to apoptosis or tumor growth inhibition.

Cat. No. Product Name Effect Purity Chemical Structure
  • HY-148439
    Daraxonrasib
    		Inhibitor 99.96%
    Daraxonrasib (RMC-6236) is an orally active, non-covalent RAS (ON) inhibitor. Daraxonrasib disrupts the interaction of wild-type or mutant RAS proteins with the RAS binding domain of BRAF, with EC50 values ranging from 28-220 nM for wild-type KRAS, NRAS, HRAS, and multiple oncogenic RAS variants. Daraxonrasib inhibits pERK. Daraxonrasib has anti-tumor activity against KRAS mutant tumors.
    Daraxonrasib
  • HY-18072
    GSK2606414
    		Inhibitor 99.91%
    GSK2606414 is a cell-permeable and orally available protein kinase R-like endoplasmic reticulum (ER) kinase (PERK) inhibitor with an IC50 of 0.4 nM.
    GSK2606414
  • HY-12495
    ISRIB (trans-isomer)
    		Inhibitor 99.49%
    ISRIB (trans-isomer) is a potent inhibitor of PERK with an IC50 of 5 nM. ISRIB potently reverses the effects of eIF2α phosphorylation (IC50=5 nM).
    ISRIB (trans-isomer)
  • HY-13820
    GSK2656157
    		Inhibitor 99.66%
    GSK2656157 is a selective and ATP-competitive inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) with an IC50 of 0.9 nM.
    GSK2656157
  • HY-119240
    CCT020312
    		Activator 99.05%
    CCT020312 is a selective EIF2AK3/PERK activator. CCT020312 elicits EIF2A phosphorylation in cells.
    CCT020312
  • HY-181087
    Anticancer agent 296
    		Activator
    Anticancer agent 296 is a potent anticancer agent that activates the PERK-eIF2α-CHOP signaling pathway to induce endoplasmic reticulum stress, thereby regulating caspase and Bcl-2 family proteins, ultimately leading to apoptosis. Anticancer agent 296 increases intracellular levels of reactive oxygen species (ROS), reduces mitochondrial membrane potential, and promotes Ca2+ release. Anticancer agent 296 suppresses cell colony formation and S-phase cell proliferation, and induces autophagy. Anticancer agent 296 is applicable for research on non-small cell lung cancer (NSCLC).
    Anticancer agent 296
  • HY-181529
    NCATS-SM0225
    		Activator
    NCATS-SM0225 is an endoplasmic reticulum-associated degradation (ERAD) inhibitor and a direct binder of VDAC1, VDAC2 and VDAC3. NCATS-SM0225 exhibits an IC50of 1.02 μM for ERAD and a Kd of 3.13 μM for human VDAC1 binding. NCATS-SM0225 disrupts cellular calcium homeostasis, enhances VDAC1-IP3R coupling and activating PERK. NCATS-SM0225 selectively kills cancer cells, exhibits tumor growth inhibitory effects in melanoma xenograft models. NCATS-SM0225 can be used for research on multiple cancers including melanoma, as well as the molecular mechanisms of ERAD and calcium homeostasis regulation.
    NCATS-SM0225
  • HY-183780
    FGFR-IN-27
    		Inhibitor
    FGFR-IN-27 is an orally active, broad-spectrum FGFR inhibitor, with an IC50 of 0.24 nM against human FGFR1, 0.71 nM against FGFR2, 0.87 nM against FGFR3, and 6.50 nM against FGFR4. FGFR-IN-27 inhibits cancer cell proliferation and blocks tumor growth. FGFR-IN-27 reduces the phosphorylation levels of AKT and ERK, induces apoptosis and ferroptosis, increases ROS levels, and decreases GSH levels. FGFR-IN-27 can be used in the research of hepatocellular carcinoma.
    FGFR-IN-27
  • HY-12661A
    AMG PERK 44
    		Inhibitor 99.67%
    AMG PERK 44 is an orally active and highly selective PERK inhibitor with an IC50 of 6 nM. AMG PERK 44 has 1000-fold and 160-fold selectivity over GCN2 (IC50=7300 nM) and B-Raf (IC50 >1000 nM), respectively. AMG PERK 44 induces autophagy.
    AMG PERK 44
  • HY-159127
    HRS-4642
    		Inhibitor 98.38%
    HRS-4642 is a high affinity, selective, long-acting, and non-covalent KRASG12D inhibitor with a Kd value of 0.083 nM. HRS-4642 inhibits the binding of KRASG12D to SOS1 or RAF1, thereby blocking the downstream MEK-ERK signaling pathway. HRS-4642 promotes Apoptosis. HRS-4642 alone or combined with Carfilzomib (HY-10455) effectively shapes the tumor microenvironment. HRS-4642 has an anti-cancer effect on pancreatic and colorectal cancers carrying the KRASG12D mutation[1][2][3].
    HRS-4642
  • HY-P9933
    Dinutuximab
    		Inhibitor ≥99.0%
    Dinutuximab (APN-311) is a chimeric human-mouse anti-GD2 monoclonal antibody. Dinutuximab can bind to GD2 on the cell surface, triggering antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity, and promoting tumor regression. Dinutuximab can inhibit the growth, invasion, and migration and induce apoptosis of tumor cells. Dinutuximab can be used in the research of tumors such as neuroblastoma and breast cancer.
    Dinutuximab
  • HY-W050044
    L-Azetidine-2-carboxylic acid
    		Activator 99.97%
    L-Azetidine-2-carboxylic acid is a proline analog. L-Azetidine-2-carboxylic acid upregulates the lipid autophagy marker LC3-II via activation of the PERK pathway. L-Azetidine-2-carboxylic acid increases pro-apoptotic BAX protein. L-Azetidine-2-carboxylic acid induces ATF6 cleavage and upregulates phosphorylated eIF2α levels. L-Azetidine-2-carboxylic acid induces ER stress, inducing protein misfolding and aggregation. L-Azetidine-2-carboxylic acid shows teratogenic, pro-inflammatory and pro-apoptotic effects.
    L-Azetidine-2-carboxylic acid
  • HY-P10102
    Kp7-6
    		Inhibitor 99.28%
    Kp7-6 is a Fas mimetic peptide and also a Fas/FasL antagonist. Kp7-6 specifically binds to Fas and FasL, disrupts receptor complexes, and blocks downstream apoptosis signaling pathways. Kp7-6 inhibits the phosphorylation of ERK1-2, induces the phosphorylation of IκBα, and activates NF-κB. Kp7-6 inhibits the activation of caspase-8, caspase-3 and JNK, and suppresses human amylin-induced β-cell apoptosis. Kp7-6 inhibits FasL-induced lymphoid cytotoxicity and apoptosis. Kp7-6 reduces local tumor FasL expression, increases CD8+Fas+ T cell infiltration, and decreases tumor volume in pancreatic neuroendocrine tumor models. Kp7-6 prevents concanavalin A-induced liver injury in mice. Kp7-6 is applicable to research related to type 2 diabetes, concanavalin A-induced hepatitis and pancreatic neuroendocrine tumors.
    Kp7-6
  • HY-P1120
    WKYMVm
    		Modulator 99.74%
    WKYMVm is a selective formylpeptide receptor 2 (FPR2) agonist. WKYMVm has a powerful anti-inflammatory effect that can reduce lung injury and spinal cord injury. WKYMVm ameliorates obesity by regulating lipid metabolism and leptin signaling. WKYMVm is involved in the regulation of immune cells by activating FPRs. WKYMVm can promote the chemotactic migration of immune cells and inhibit the apoptosis of phagocytes. In addition, WKYMVm may play a favorable or unfavorable role in tumors, depending on the type of tumor.
    WKYMVm
  • HY-P3419
    PAMP-12 (unmodified)
    		99.40%
    PAMP-12 (unmodified) is an endogenous peptide and is a MrgX2 agonist. PAMP-12 (unmodified) can reduce cAMP accumulation, increase Ca2+ levels, enhance beta-arrestin recruitment, decrease IP-1, and increases phosphoERK. PAMP-12 (unmodified) can elicit hypotension through inhibiting catecholamine secretion from sympathetic nerve endings and adrenal chromaffin cells. PAMP-12 (unmodified) can be used for the research of hypotension and ulcerative colitis.
    PAMP-12 (unmodified)
  • HY-137207
    MK-28
    		Activator 99.88%
    MK-28 is a potent and selective PERK activator. MK-28 exhibits remarkable pharmacokinetic properties and high BBB penetration in mice.
    MK-28
  • HY-N6664
    Gum arabic
    		Activator
    Gum Arabic is an orally active complex branched polysaccharide. Gum Arabic can be isolated from the Acacia senegal tree. Gum Arabic upregulates the expression of maturation markers (CD86, CD40, and CD54), promotes ERK1/2 phosphorylation, and inhibits Apoptosis. Gum Arabic exhibits antimalarial effects against Plasmodium berghei ANKA. Gum Arabic exhibits hepatoprotective, renal, and cardiovascular protective activities. Gum Arabic improves obesity. Gum Arabic is commonly used as a stabilizer and thickener. Gum Arabic can be used in the research of brain tumor imaging.
    Gum arabic
  • HY-P99828
    Cofetuzumab
    		Modulator 99.31%
    Cofetuzumab (PF-06523435) is a humanized IgG1-κ monoclonal antibody targeting PTK7. The expression system of Cofetuzumab is typically CHO (Chinese hamster ovary) cells. Cofetuzumab downregulates PTK7 expression, modulates its downstream signaling pathways, and inhibits tumor sphere formation of ovarian cancer cells. Cofetuzumab can be used to synthesize the ADC molecule Cofetuzumab pelidotin (HY-P99829). Cofetuzumab is applicable to the research of tumors such as ovarian cancer.
    Cofetuzumab
  • HY-N0265
    Asperosaponin VI
    		99.62%
    Asperosaponin VI is a saponin component from Dipsacus asper. Asperosaponin VI induces osteoblast differentiation through the BMP-2/p38 and ERK1/2 signaling pathways. Asperosaponin VI protects against hypoxia-induced cardiomyocyte apoptosis by activating the PI3K/Akt and CREB pathways. Additionally, Asperosaponin VI also has antidepressant and wound-healing-promoting activities.
    Asperosaponin VI
  • HY-N1500
    Pulegone
    		Inhibitor 99.57%
    Pulegone is a monoterpene ketone compound widely present in the essential oils of many plants. Pulegone can also be used as a bird repellent. Pulegone has multiple activities such as anti-inflammatory, antibacterial, antifungal, and anti-hyperalgesic effects. Pulegone is particularly effective against bacteria of the Salmonella species.
    Pulegone
Cat. No. Product Name / Synonyms Application Reactivity