Lidocaine, an amide local anesthetic, has anti-inflammatory properties in vitro and in vivo, possibly due to an attenuation of pro-inflammatory cytokines, intracellular adhesion molecule-1 (ICAM-1), and reduction of neutrophils influx.Target: Lidocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery. Lidocaine, the first amino amide–type local anesthetic, was first synthesized under the name xylocaine by Swedish chemist Nils Lofgren in 1943. His colleague Bengt Lundqvist performed the first injection anesthesia experiments on himself.Lidocaine is approximately 95% metabolized (dealkylated) in the liver by CYP3A4 to the pharmacologically-active metabolites monoethylglycinexylidide (MEGX) and then subsequently to the inactive glycine xylidide. MEGX has a longer half life than lidocaine but also is a less potent sodium channel blocker. The elimination half-life of lidocaine is approximately 90–120 minutes in most patients. This may be prolonged in patients with hepatic impairment (average 343 minutes) or congestive heart failure (average 136 minutes).
ERK5-IN-5 (compound 4a) is an ERK5 kinase inhibitor with anticancer activity. ERK5-IN-5 exhibits good anti-proliferative activity with the IC50 value of 6.23 µg/mL for A549 cells[1].
HIOC is a potent and selective activator of TrkB (tropomyosin related kinase B) receptor. HIOC can pass the blood-brain and blood-retinal barriers.HIOC activates TrkB/ERK pathway and decreases neuronal cell apoptosis. HIOC attenuates early brain injury after SAH (subarachnoid hemorrhage). HIOC shows protective activity in an animal model for light-induced retinal degeneration[1][2][3].
MY-673 is a colchicine binding site inhibitor (CBSI), that inhibits tubulin polymerization. MY-673 inhibits the ERK signaling pathway, which in turn affects SMAD4 protein expression levels in the TGF-β/SMAD pathway. MY-673 inhibited cell proliferation, migration and induced apoptosis in vivo and in vitro[1].
Rutin hydrate is a flavonol glycoside, able to cross the blood-brain barrier, and acts by inhibiting JNK and ERK1/2 activation and activating mTOR signalling.
2,5-Dihydroxyacetophenone, isolated from Rehmanniae Radix Preparata, inhibits the production of inflammatory mediators in activated macrophages by blocking the ERK1/2 and NF-κB signaling pathways[1].
mSIRK (G-Protein βγ Binding Peptide) is an cell-permeable activator of ERK1/2, with EC50 of 2.5-5 μM. mSIRK disrupts the interaction between α and βγ subunits and promotes α subunit dissociation without stimulating nucleotide exchange[1].
Patritumab (Human Anti-ERBB3 Recombinant Antibody) is a neutralizing monoclonal antibody to ERBB3. Patritumab shows a synergy with Cetuximab (HY-P9905), potently inhibits the phosphorylation of EGFR, HER2, HER3, ERK, and Akt. Patritumab also induces cell apoptosis and suppresses the growth of pancreatic, non-small cell lung cancer, and colorectal cancer xenograft tumors[1].
Muramyl dipeptide (MDP) is a synthetic immunoreactive peptide, consisting of N-acetyl muramic acid attached to a short amino acid chain of L-Ala-D-isoGln. Muramyl dipeptide is an inducer of bone formation through induction of Runx2. Muramyl dipeptide directly enhances osteoblast differentiation by up-regulating Runx2 gene expression through MAPK pathways. Muramyl dipeptide indirectly attenuates osteoclast differentiation through a decreased RANKL/OPG ratio[1].
6,8-Diprenylorobol, a prenylated isoflavone, is a nature product that could be isolated from the leaves of Cudrania tricuspidata. 6,8-Diprenylorobol antiproliferative effect and induces apoptosis through activation of p53 and generation of ROS[1][2].
Nitidine chloride, a potential anti-malarial lead compound derived from Zanthoxylum nitidum (Roxb) DC, exerts potent anticancer activity through diverse pathways, including inducing apoptosis, inhibiting STAT3 signaling cascade, DNA topoisomerase 1 and 2A, ERK and c-Src/FAK associated signaling pathway. Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK and NF-kB pathway[1][2][3][4][5][6].
Lidocaine-d6 (hydrochloride) is deuterium labeled Lidocaine (hydrochloride). Lidocaine hydrochloride (Lignocaine hydrochloride) inhibits sodium channels involving complex voltage and using dependence[1]. Lidocaine hydrochloride decreases growth, migration and invasion of gastric carcinoma cells via up-regulating miR-145 expression and further inactivation of MEK/ERK and NF-κB signaling pathways. Lidocaine hydrochloride is an amide derivative and a drug to treat ventricular arrhythmia and an effective tumor-inhibitor[2].
A small molecule inhibitor of guanine nucleotide exchange factor (GEF) catalytic activity that binds to SOS1 (Kd=14.7 uM) and disrupts GEF-Ras interaction; dose-dependently disrupts the SOS1-Ras interaction by competitively inhibiting the binding of SOS1cat to GDP-bound H-Ras in a microscale thermophoresis assay; dose-dependently inhibits Ras activation and downstream ERK activation mediated through EGFR-SOS1-Ras-Raf1-MEK-ERK signaling, specifically inhibits wild-type mouse embryonic fibroblast growth but not the growth of oncogenic H-Ras(G12V)-expressing mouse embryonic fibroblasts; inhibits Ras signaling and growth of pancreatic and prostate cancer cells.
Isoprocurcumenol is a guaiane type sesquiterpene, that can be isolated from Curcuma comosa. Isoprocurcumenol can activate EGFR signaling. Isoprocurcumenol increases the phosphorylation of ERK and Akt. Isoprocurcumenol promotes the proliferation of keratinocytes[1][2][3].
ERK1/2 inhibitor 9 (Probe 1) is a covalent ERK1/2 inhibitor. ERK1/2 inhibitor 9 shows sub-micromolar activity in cells (A375 GI50=0.47 μM). ERK1/2 inhibitor 9 causes the downregulation of phospho-ERK1/2. ERK1/2 inhibitor 9 tagged trans-cyclo-octene (TCO) and Tz-Thalidomide (tetrazine tagged Thalidomide) can form the corresponding ERK-CLIPTAC to elicit degradation of ERK1/2[1].
ACA-28 (compound 2a) is a potent ERK MAPK signaling modulator. ACA-28 selectively inhibits cancer cell growth by inducing apoptosis with ERK hyperactivationACA-28 inhibits cell growth of melanoma cells (SK-MEL-28) and normal melanocytes (NHEM), with IC50 values of 5.3 and 10.1 μM, respectively[1].
Vitisin A has antioxidative, anticancer, antiapoptotic, neuroprotective and anti-inflammatory effects. Vitisin A inhibits LPS-induced NO and iNOS production via down-regulation of ERK1/2 and p38 and the NF-κB signal pathway. Vitisin A also inhibits adipocyte differentiation. Vitisin A is a resveratrol tetramer that can be isolated from Vitis vinifera roots[1][2][3].
H-Ile-Lys-Val-Ala-Val-OH is one of the most potent active sites of laminin-1. H-Ile-Lys-Val-Ala-Val-OH promotes cell adhesion, neurite outgrowth, and tumor growth. H-Ile-Lys-Val-Ala-Val-OH stimulates BMMSC population growth and proliferation by activating MAPK/ERK1/2 and PI3K/Akt signalling pathways[1][2].
Hypothemycin, a fungal polyketide, is a multikinase inhibitor with Kis of 10/70 nM, 17/38 nM, 90 nM, 900 nM/1.5 μM, and 8.4/2.4 μM for VEGFR2/VEGFR1, MEK1/MEK2, FLT-3, PDGFRβ/PDGFRα, and ERK1/ERK2, respectively[1][2].
Longdaysin is a CK1α, CK1δ, and extracellular signal-regulated kinase 2 (ERK2) inhibitor with IC50s of 5.6 µM, 8.8 µM, and 52 µM, respectively[1][2].
trans-Zeatin-d5 is deuterium labeled trans-Zeatin. trans-Zeatin is a plant cytokinin, which plays an important role in cell growth, differentiation, and division; trans-Zeatin also inhibits UV-induced MEK/ERK activation.
ERK-IN-4 is an ERK inhibitor binds preferentially to ERK2 with a Kd of 5 μM. ERK-IN-4 specificity inhibits ERK Rsk-1 and Elk-1 phosphorylation. ERK-IN-4 has little effect on ERK protein phosphorylation by its upstream activator MEK1/2[1].
NMDAR/TRPM4-IN-2 (compound 8) is a potent NMDAR/TRPM4 interaction interface inhibitor. NMDAR/TRPM4-IN-2 shows neuroprotective activity. NMDAR/TRPM4-IN-2 prevents NMDA-induced cell death and mitochondrial dysfunction in hippocampal neurons, with an IC50 of 2.1 μM. NMDAR/TRPM4-IN-2 protects mice from MCAO-induced brain damage and NMDA-induced retinal ganglion cell loss[1].
SCH772984 potently inhibits ERK1 and ERK2 activity with IC50s of 4 and 1 nM, respectively.
ERK1/2 inhibitor 6 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 6 has the potential for the research or prevention of cancer, inflammation or other proliferative diseases (extracted from patent WO2021063335A1, compound 1)[1].
ERK5-IN-3 (compound 33j) is a potent and selective ERK5 (extracellular signal-related kinase 5) inhibitor, with an IC50 of 6 nM. ERK5-IN-3 shows antiproliferation activity against Hela cells, with an IC50 of 31 nM[1].
β-Neo-Endorphin is an endogenous opioid peptide. β-Neo-Endorphin is a hypothalamic “big” Leu-enkephalin of porcine origin. β-Neo-Endorphin shows activation of the Erk1/2, MMP-2 and MMP-9[1][2].
Honokiol is a bioactive, biphenolic phytochemical that possesses potent antioxidative, anti-inflammatory, antiangiogenic, and anticancer activities by targeting a variety of signaling molecules. It inhibits the activation of Akt and enhances the phosphorylation of ERK1/ERK2.
Tauroursodeoxycholate-d4 is deuterium labeled Tauroursodeoxycholate. Tauroursodeoxycholate (Tauroursodeoxycholic acid) is an endoplasmic reticulum (ER) stress inhibitor. Tauroursodeoxycholate significantly reduces expression of apoptosis molecules, such as caspase-3 and caspase-12. Tauroursodeoxycholate also inhibits ERK.