BIX02188 is a potent MEK5-selective inhibitor with an IC50 of 4.3 nM. BIX02188 inhibits ERK5 catalytic activity, with an IC50 of 810 nM.
Ravoxertinib (GDC-0994) is an orally bioavailable ERK kinase inhibitor with an IC50 of 6.1 nM and 3.1 nM for ERK1 and ERK2, respectively.
ERK1/2 inhibitor 7 is a potent ERK inhibitor with an IC50 of 0.94 nM for ERK2 (WO2021110168A1, WX006)[1].
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].
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].
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.
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].
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].
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].
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.
(E)-Osmundacetone is the isomer of Osmundacetone. Osmundacetone significantly suppresses the phosphorylation of MAPKs, including JNK, ERK, and p38 kinases. Osmundacetone has a neuroprotective effect against oxidative stress[1].
Urolithin B is one of the gut microbial metabolites of ellagitannins, and has anti-inflammatory and antioxidant effects. 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[1][2].
Bohemine is a purine analogue and is a synthetic and selective CDK inhibitor with IC50s of 4.6 μM, 83 μM, and 2.7 μM for Cdk2/cyclin E, Cdk2/cyclin A, and Cdk9/cyclin T1, respectively. Bohemine also inhibits ERK2 with an IC50 of 52 μM and has less inhibitory effect on CDK1, CDK4 and CDK6. Bohemine has a broad spectrum anti-cancer activities[1][2].
ERK5-IN-4 (compound 34b) is a potent and selective inhibitor of extracellular signal-related kinase 5 (ERK5). ERK5-IN-4 inhibits ERK5 (full-length) and truncated ERK5 (ERK5 ΔTAD) kinase activity in HEK293 cells with an IC50 of 77 nM and 300 nM, respectively[1].
POP-3MB (compound 1b) is an ICMT inhibitor (IC50: 2.5 μM). POP-3MB changes the subcellular localization of K-Ras and inhibits Ras activation. POP-3MB also inhibits Erk phosphorylation[1].
Pluripotin is a dual inhibitor of ERK1 and RasGAP with KDs of 98 nM and 212 nM, respectively. Pluripotin also inhibits RSK1, RSK2, RSK3, and RSK4 with IC50s of 0.5, 2.5, 3.3, and 10.0 µM, respectively.
Emodic acid (NSC624610) is an anthraquinone compound isolated from A. microcarpus, which can inhibit the proliferation of cancer cells by inhibiting the activity of NF-κB. Emodic acid can also inhibit the phosphorylation of p38, ERK and JNK, the secretion of tumor-promoting cytokines IL-1β and IL-6, and the expression of VEGF and MMP, thereby inhibiting the invasion and migration potential of cancer cells[1].
ERK-IN-7 (Example 10), an analogue of SHR2415 (HY-151367), is a potent ERK inhibitor with IC50 of 5 nM and 7 nM against ERK1 and ERK2, respectively[1].
XMD8-92 is a highly selective ERK5/BMK1 inhibitor with dissociation constant (Kd) value of 80 nM.