Piperlongumine is a natural alkaloid isolated from Piper longum Linn[1], possesses ant-inflammatory, antibacterial, antiangiogenic, antioxidant, antitumor, and antidiabetic activities[2]. Piperlongumine induces ROS, and induces apoptosis in cancer cell lines[1]. Piperlongumine shows anti-cardiac fibrosis activity, suppresses myofibroblast transformation via suppression of the ERK1/2 signaling pathway[2].
ADTL-EI1712 is a potent, orally active, and selective dual-target inhibitor of ERK1 and ERK5, inhibition rates of ERK1/5 at 1 μM are 93.54% and 89.35%, respectively. ADTL-EI1712 can induce regulated cell death, a form of cell death that relies on the activation of genetically encoded machinery, to overcome compensatory mechanism in specific cancer cells in vitro and in vivo[1].
STE-MEK1(13) (Ste-MPKKKPTPIQLNP-NH?) is a cell permeable ERK1/2 inhibitor (IC50: 13-30?μM). STE-MEK1(13) inhibits ERK1/2 phosphorylation[1][2].
JWG-071 is the first reported kinase-selective chemical probe for ERK5. JWG-071 improves ERK5 activity and BRD4 selectivity. JWG-071 will be a much-needed chemical probe for deconvoluting ERK5 and BRD4 pharmacology[1].
Hirsutenone is an active botanical diarylheptanoid present in Alnus species and exhibits many biological activities, including anti-inflammatory, anti-tumor promoting and anti-atopic dermatitis effects. Hirsutenone attenuates adipogenesis by binding directly to PI3K and ERK1 in a non-ATP competitive manner. Hirsutenone can be used for the study of obesity[1].
ERK Inhibitor II (Negative control) is an effective inhibitor of extracellular signal-regulated kinase (ERK). ERK Inhibitor II (Negative control) inhibits the activation of insulin receptor, which can be used in the study of diabetes[1][2].
FR 180204 is an ATP-competitive, selective ERK inhibitor with Ki of 0.31 μM and 0.14 μM for ERK1 and ERK2, respectively.
Cearoin, isolated from Dalbergia odorifera, increases autophagy and apoptosis through the production of ROS and the activation of ERK[1].
Albanol B is an arylbenzofuran derivative which can be isolated from mulberries. Albanol B exhibits anti-Alzheimer's disease, anti-bacterial and antioxidant activities. Albanol B inhibits cancer cells proliferation, down-regulates CDK1 expression. Albanol B also induces cell cycle arrest at G2/M and apoptosis. And Albanol B induces mitochondrial ROS production and increases the phosphorylation levels of AKT and ERK1/2[1].
CHPG sodium salt is a selective mGluR5 agonist, and attenuates SO2-induced oxidative stress and inflammation through TSG-6/NF-κB pathway in BV2 microglial cells[1]. CHPG sodium salt protects against traumatic brain injury (TBI) in vitro and in vivo by activation of the ERK and Akt signaling pathways.[2].
MAPK-IN-1 (Compound 2) is a MAPK signaling pathway inhibitor. MAPK-IN-1 exhibits AChE inhibitory activity with an IC50 of 23.84 μM. MAPK-IN-1 shows anti-neuroinflammatory and neuroprotective activity and can be used for Alzheimer's disease research[1].
Theaflavin 3,3'-digallate (TF3), the typical pigment in black tea, is a good antitumor agent. Theaflavin 3,3'-digallate is generally regarded as the effective component for the inhibitory effects against carcinogenesis without adverse side effects by affecting multiple signal transduction pathways, such as upregulating p53 and p21, inhibiting phosphorylation of the cell survival protein Akt and MAPK pathway, downregulation of NF-κB, shifting the ratio between pro-/antiapoptotic proteins. Theaflavin 3,3'-digallate causes a rapid and sustained decrease in phospho-ERK1/2 and -MEK1/2 protein expression. Theaflavin 3,3'-digallate inhibits HCT116 cell growth with an IC50 of 17.26 μM[1].
Pseudocoptisine acetate, a quaternary alkaloid with a benzylisoquinoline skeleton, is isolated from the tubers of Corydalis turtschaninovii. Pseudocoptisine acetate shows anti-inflammatory properties[1].
CK2/ERK8-IN-1 is a dual casein kinase 2 (CK2) (Ki of 0.25 µM) and ERK8 inhibitor with IC50s of 0.50 μM. CK2/ERK8-IN-1 also binds to PIM1, HIPK2 (homeodomain-interacting protein kinase 2), and DYRK1A with Kis of 8.65 µM, 15.25 µM, and 11.9 µM, respectively. CK2/ERK8-IN-1 has pro-apoptotic efficacy[1].
Cafestol, one of the major components of coffee, is a coffee-specific diterpene from. Cafestol is a ERK inhibitor for AP-1-targeted activity against PGE2 production and the mRNA expression of cyclooxygenase (COX)-2 in LPS-activated RAW264.7 cells. Cafestol has strong inhibitory activity on PGE2 production by suppressing the NF-kB activation pathway. Cafestol contributes to its beneficial effects through various biological activities such as chemopreventive, antitumorigenic, hepatoprotective, antioxidative and antiinflammatory effects[1].
epi-Eriocalyxin A (Epieriocalyxin A), a diterpenoid isolated from Isodon eriocalyx, induces colon cancer apoptosis. epi-Eriocalyxin A also inhibits ERK1/2 and JNK activation, which suppresses Bcl-2 expression[1].
SY-LB-35 is a potent bone morphogenetic protein (BMP) receptor agonist. SY-LB-35 can stimulate significant increases in cell number and cell viability in the C2C12 myoblast cell line, and causes shifts towards the S and G2/M phases of the cell cycle. SY-LB-35 stimulates canonical Smad and non-canonical PI3K/Akt, ERK, p38 and JNK intracellular signaling pathways[1].
AZA197 is a selective small molecule inhibitor of Cdc42.AZA197 suppresses colon cancer cell proliferation, cell migration, invasion and increases apoptosis by down-regulating the PAK1 and ERK signaling pathways in vitro. AZA197 reduces tumor growth and significantly increases mouse survival in SW620 tumor xenografts[1].
ERK1/2 inhibitor 3 is a potent inhibitor of ERK1/2. Mitogen-activated protein kinase (MAPK) plays an extremely important role in the signal transduction pathway, and extracellular signal regulated kinase (ERK) is a member of the MAPK family. ERK1/2 inhibitor 3 has the potential for the research or prevention of cancer, inflammation or other proliferative diseases (extracted from patent WO2021218912A1, compound 1)[1].
Gypenoside L is a saponin that can be found in Gynostemma pentaphyllum. Gypenoside L increases the SA-β-galactosidase activity, promotes the production of senescence-associated secretory cytokines. Gypenoside L also can activate p38 and ERK MAPK pathways and NF-κB pathway to induce senescence. Gypenoside L exhibits anti-tumor and anti-inflammatory activities[1][2].
Cudraflavone B is a prenylated flavonoid with anti-inflammatory and anti-tumor properties. Cudraflavone B is also a dual inhibitor of COX-1 and COX-2. Cudraflavone B blocks the translocation of nuclear factor κB (NF-κB) from the cytoplasm to the nucleus in macrophages. Thus, Cudraflavone B inhibits tumor necrosis factor α (TNFα) gene expression and secretion. Cudraflavone B also triggers the mitochondrial apoptotic pathway, activates NF-κB, the MAPK p38, and ERK, and induced the expression of SIRT1. Thus Cudraflavone B inhibits the growth of human oral squamous cell carcinoma cells[1][2].
ERK5-IN-6 (compound 5J) is an ERK5 kinase inhibitor with anticancer activity. ERK5-IN-6 exhibits good anti-proliferative activity with the IC50 value of 4.56 µg/mL for A549 cells[1].
Dehydrocrenatidine, a β-carboline alkaloid that can be isolated from Picrasma quassioides. Dehydrocrenatidine induces cell Apoptosis by activates ERK and JNK. Dehydrocrenatidine inhibits invasion and migration of cancer cells, it also suppresses neuronal excitability to exert analgesic effects[1][2].
Pamoic acid is a potent GPR35 agonist with an EC50 of 79 nM. Pamoic acid exhibits neuroprotective and anti-inflammatory properties[1][2].
Enniatin A1 isolated from Fusarium mycotoxins is a cyclic hexadepsipeptide consisting of alternating D-α-hydroxyisovaleric acids and N-methyl-L-amino acids. Enniatin A1 possesses anticarcinogenic properties by induction of apoptosis and disruption of ERK signalling pathway. Enniatin A1 inhibits ACAT with an IC50 of 49 μM in rat liver microsomes[1].
Astragaloside IV, an active component isolated from Astragalus membranaceus, suppresses the activation of ERK1/2 and JNK, and downregulates matrix metalloproteases (MMP)-2, (MMP)-9 in MDA-MB-231 breast cancer cells.
Enniatin B is a Fusarium mycotoxin. Enniatin B inhibits acyl-CoA: cholesterol acyltransferase (ACAT) activity with an IC50 of 113 μM in an enzyme assay using rat liver microsomes[1]. Enniatins B decreases the activation of ERK (p44/p42)[2].
Asperulosidic Acid (ASPA), a bioactive iridoid glycoside, is extracted from the herbs of Hedyotis diffusa Willd. Asperulosidic Acid (ASPA) has anti-tumor, anti-oxidant, and anti-inflammatory activities[1].ASPA is related to the inhibition of inflammatory cytokines (TNF-α, IL-6) and mediators via suppression of the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways[2].
ERK1/2 inhibitor 5 is a potent inhibitor of ERK1/2. Mitogen-activated protein kinase (MAPK) plays an extremely important role in the signal transduction pathway, and extracellular signal regulated kinase (ERK) is a member of the MAPK family. ERK1/2 inhibitor 5 has the potential for the research or prevention of cancer, inflammation or other proliferative diseases (extracted from patent WO2020238776A1)[1].
Gardenin A is an orally active and synthetic PMF analogue with the neurotrophic effect for neurite outgrowth and neuronal differentiation. Gardenin A promotes neuritogenesis via activating MAPK/ERK, PKC, and PKA, but not TrkA, CREB signaling pathways. Gardenin A also has sedative, anxiolytic, antidepressant, and anticonvulsant effects[1][2].