extracellular signal regulated kinases

MK-8353 (SCH900353) is a potent, selective, and orally available inhibitor of ERK1 2 with IC50 values of 23.0 nM and 8.8 nM, respectively.

Lidocaine hydrochloride (Lignocaine hydrochloride) is a local anesthetic and cardiac depressant used as an antiarrhythmic agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.

Tauroursodeoxycholate sodium (TUDC) is an endoplasmic reticulum (ER) stress inhibitor, used for the treatment of gallstones and liver cirrhosis.

Honokiol (NSC-293100) is the active principle of magnolia extract. It inhibits the activation of Akt and enhances the phosphorylation of ERK1 ERK2.

Lidocaine (Alphacaine) is an amide local anesthetic with anti-inflammatory properties in vitro and in vivo. It has this functions perhaps due to an attenuation of intracellular adhesion molecule-1 (ICAM-1), pro-inflammatory cytokines, and reduction of neutrophils influx.

Urolithin B is one of the gut microbial metabolites of ellagitannins and is found in diverse plant foods, including pomegranates, berries, walnuts, tropical fruits, and medicinal herbs. Urolithin B inhibits NF-κB activity by reducing the phosphorylation and degradation of IκBα, and suppresses the phosphorylation of JNK, ERK, and Akt, and enhances the phosphorylation of AMPK. Urolithin B is also a regulator of skeletal muscle mass. Urolithin B has anti-inflammatory and antioxidant effects.

Tauroursodeoxycholate (UR 906), also known as ursodoxicoltaurine, is a highly hydrophilic tertiary bile acid that is produced in humans at a low concentration. Tauroursodeoxycholate is the more hydrophilic form of ursodeoxycholic acid, which is the more abundant naturally produced bile acid in humans.Tauroursodeoxycholate is being investigated for use in several conditions such as Primary Biliary Cirrhosis (PBC), insulin resistance, amyloidosis, Cystic Fibrosis, Cholestasis, and Amyotrophic Lateral Sclerosis.

Astragaloside IV (AS-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. Astragaloside IV is a bioactive saponin first isolated from the dried plant roots of the genus Astragalus, which is used in traditional Chinese medicine.1 It dose-dependently inhibits human adenovirus type 3 (HAdV-3) in A549 cells (IC50 = 23 μM; LC50 = 865 μM).It inhibits replication of HAdV-3 and decreases HAdV-3-induced apoptosis. It has diverse protective effects for the cardiovascular, immune, digestive, and nervous systems. In particular, it reduces myocardial infarct size in dogs when administered prior to coronary ligation and reduces reperfusion arrhythmias in isolated rat hearts.

1. 2,5-Dihydroxyacetophenone (Quinacetophenone) possess anti-anxiety, and neuroprotective qualities. 2. 2,5-Dihydroxyacetophenone (Quinacetophenone) reatment can induce a sustained activation of JNK, ERK1 2, and p38 MAPKs, it also can potentiate the pro-apoptotic and anti-proliferative effects of bortezomib in U266 cells. 3. 2,5-Dihydroxyacetophenone (Quinacetophenone) has anti-inflammatory activity in activated macrophages, raising the possibility that this compound has a therapeutic potential for inflammatory conditions. 4. 2,5-Dihydroxyacetophenone (Quinacetophenone) is an uncompetitive inhibitor of murine tyrosinase (K(I) 0.28mm), it strongly inhibits both melanogenesis and cellular tyrosinase activity in vitro in 3-isobutyl-1-methylxanthin-stimulated B16 mouse melanoma cells or in vivo in zebrafish and mouse models.

TBHQ (tert-Butylhydroquinone) is an antioxidant that induces an antioxidant response through the redox-sensitive transcription factor Nrf2.

Lidocaine Hydrochloride hydrate is an amide local anesthetic, has anti-inflammatory property.

Epieriocalyxin A can suppress Caco-2 colon cancer cell growth. It could be a potential drug for colon cancer therapy in the future.

EF24 (3,5-Bis[(2-fluorophenyl)Methylene]-4-piperidinone) treatment increases the levels of activated caspase 3 and 9, and decreases the phosphorylated forms of MEK1 and ERK. EF24 shows potent anti-tumor activity in oral squamous cell carcinoma (OSCC) via deactivation of the MAPK/ERK signaling pathway.

Yoda 1 is an agonist of the Piezo1 channel that agonizes human- and mouse-derived Piezo1 (EC50=17.1 26.6 μM). Yoda 1 is also an inhibitor of glycine transporter protein 2 (GlyT2).

Temuterkib (LY3214996) is a potent and selective, orally available inhibitor of the extracellular signal-regulated kinase (ERK) 1 and 2, with potential antineoplastic activity.

Asperulosidic acid (ASPA) has anti-tumor, anti-oxidant, and anti-inflammatory activities. 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.

Rineterkib (ERK-IN-1) is an inhibitor of RAF and ERK1/2 activating mutations in the MAPK pathway.

Ulixertinib (VRT752271) (BVD-523, VRT752271) is an effective and reversible ERK1 ERK2 inhibitor. The IC50 of Ulixertinib is less than 0.3 nM for ERK2.

Bohemine is a cyclin-dependent kinase inhibitor.

PD98059 is an MEK inhibitor that inhibits MEK1 and MEK2 (IC50=2/50 μM) and is non-ATP-competitive. PD98059 is also antagonistic as a ligand for AHR. PD98059 inhibits autophagy.

SCH772984 is an ERK inhibitor that inhibits ERK1 and ERK2 (IC50=4 1 nM) and is highly selective and ATP-competitive. SCH772984 exhibits antitumor activity against BRAF or RAS mutant cells.

FR 180204 is a potent and selective ATP-competitive inhibitor of ERK1 and ERK2.

Ravoxertinib (GDC-0994) is an efficacious, orally available ERK1 2 inhibitor with an IC50 of 1.1 0.3 nM.

Piperlongumine (Piplartine) is a natural alkaloid from Piper longum L. It selectively kills cancer cells and strengthens the level of reactive oxygen species (ROS).

XMD8-92 is an effective and specific BMK1/ERK5 inhibitor (Kd: 80 nM).

KO-947 is a potent and specific ERK1 2 kinase inhibitor.

CC-90003 is a selective inhibitor of ERK 1 2. It has antitumor activity.

AX-15836 is an inhibitor of ERK5 (IC50 : 8 nM).

XMD17-109 (ERK5-IN-1) is a new selective ERK-5 inhibitor (EC50: 4.2 uM, HEK293 cells).

AG126 (Tyrphostin AG126) selectively inhibits the phosphorylation of ERK1 (p44) and ERK2 (p42) at 25-50 μM. It blocks the production of TNF-α in vitro2 and in vivo, attenuating signaling through NF-κB, the induced expression of COX-2 and iNOS, and the inflammatory response in diverse animal models. AG-126 weakly inhibits epidermal GFRK (IC50: 450 μM) and platelet-derived GFRK (IC50 > 100 μM).

Mogrol, a biometabolite of mogrosides, functions by inhibiting the ERK1 2 and STAT3 pathways, diminishing CREB activation, and activating AMPK signaling.

BIX02189 is a potent and selective inhibitor of MEK5 and ERK5 (IC50: 1.5 nM and 59 nM).

LM22B-10, an activator of the TrkB TrkC neurotrophin receptor, can induce activation of TrkB, TrkC, ERK, and AKT both in vitro and in vivo.

ERK5-IN-1 is a potent ERK5 inhibitor (IC50: 87 nM) and also inhibits LRRK2[G2019S] (IC50: 26 nM).

Longdaysin is an inhibitor of CK1α and CK1δ (IC50s: 5.6 8.8 µM). It also can inhibit ERK2 (IC50: 52 µM).

6-OAU (GTPL5846)(GTPL5846; 6-n-octylaminouracil) is a surrogate agonist of GPR84; activates human GPR84 in the presence of Gqi5 chimera in HEK293 cells with an EC50 of 105 nM in the PI assay.

Gynosaponin TN-2, demonstrating anti-Parkinsonian activity, mitigates L-DOPA (100 and 200 μM)-induced apoptotic cell death in pheochromocytoma 12 cells through the modulation of extracellular signal-regulated protein kinases 1 and 2 activation.

SEW 2871 is an orally available, highly selective S1P1 agonist with an EC50 of 13.8 nM.It reduces the number of lymphocytes in the blood and is used in studies related to diabetes, Alzheimer's disease, liver fibrosis, and inflammation. It activates ERK, Akt and Rac signaling pathways and induces S1P1 internalization and recycling.

TRPM4 inhibitor 8 is an inhibitor of Transient receptor potential melastatin 4(TRPM4) which contributes to viability, migration, cell cycle shift, and adhesion.

Isoacteoside has the anti-inflammatory effect, mediated by action on caspase-1, mitogen-activated protein kinases (c-Jun N-terminal kinase, p38, extracellular signal-regulated protein kinase) and nuclear factor-kappa B pathways.

Sulforaphene is a natural product isolated from radish seeds, exhibits an ED50 against velvetleaf seedlings approximately 2 x 10 -4 M. Sulforaphene promotes cancer cells apoptosis and inhibits migration via inhibiting EGFR, p-ERK1 2, NF‐κB and other signa

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.

1. Corynoxeine is a potent ERK1 2 inhibitor of key PDGF-BB-induced VSMC proliferation and may be useful in the prevention and treatment of vascular diseases and restenosis after angioplasty.

Gypenoside L inhibits autophagic flux and induces cell death in human esophageal cancer cells through endoplasm reticulum stress-mediated Ca2+ release. It also inhibit non-small cell lung carcinoma A549 cell inhibitory activity.

Loureirin B can downregulate the expression of fibrosis-related molecules by regulating MMPs and TIMPs levels, inhibit scar fibroblast proliferation and suppress TGF-β1-induced fibrosis, during which TGF-β1 Smad2 3 pathway is likely involved.

Deltonin has an inhibition of ERK1 2 and AKT activation. Deltonin shows cytotoxicity against human HepG2 cells (IC50: 7.66 μM), mouse C26 cells (IC50: 1.22 μM), and human MDA-MB-231 cells (IC50: 1.58 μM).

Tenuifoliside A has anti-apoptotic , neuroprotective activity. And tenuifoliside A has anti-inflammatory effect, which is mediated by the inhibition of the NF-κB and MAPK pathways.

Methylnissolin is a natural product isolated from Astragalus membranaceus that inhibits platelet-derived growth factor (PDGF)-BB-induced cell proliferation with an IC50 of 10 μM. It inhibits PDGF-BB-induced vascular smooth muscle cell proliferation by inhibiting the ERK1 2 MAP kinase cascade. It also inhibits PDGF-BB-induced phosphorylation of extracellular signal-regulated kinase 1 2 (ERIC1 2) mitogen-activated protein (MAP) kinases and has antibacterial and anticancer effects.