RLX-33 is a potent, selective and blood-brain barrier (BBB) penetrant relaxin family peptide 3 (RXFP3) antagonist, also blocks relaxin-3-induced ERK1/2 phosphorylation, with IC50 values of 2.36 μM for RXFP3, 7.82 and 13.86 μM for ERK1 and ERK2 phosphorylation, respectively. RLX-33 can block the stimulation of food intake induced by the RXFP3-selective agonist R3/I5 in rats. RLX-33 can be used for the research of metabolic syndrome[1].
Enniatin B1 is a Fusarium mycotoxin. Enniatin B1 inhibits acyl-CoA: cholesterol acyltransferase (ACAT) activity with an IC50 of 73 μM in an enzyme assay using rat liver microsomes[1]. Enniatin B1 crosss the blood-brain barrier[2]. Enniatin B1 decreases the activation of ERK (p44/p42). Enniatin B1 inhibits moderately TNF-α-induced NF-κB activation[3].
VX-11e is a potent, selective, and orally bioavailable inhibitor of ERK with Ki < 2 nM.
Prolylserine, a dipeptide, is an inhibitor of melanogenesis production in Mel-Ab cells. Prolylserine decreases expression of microphthalmia-associated transcription factor (MITF) and tyrosinase, induces phorphosylation of ERK, but not cAMP response element binding protein (CREB)[1].
I-287 is a potent, selective, orally active inhibitor of PAR2, negative PAR2 allosteric modulator, inhibits PAR2-mediated activation of Gq and G12/13 but not Gi/o proteins (IC50=45-390 nM);I-287 is a negative allosteric modulator (NAM) and not an orthosteric competitive antagonist of hPAR2.I-287 inhibits PAR2-mediated activation of DAG/Ca2+/PKC and RhoA/SRF-RE, as well as FAK and ERK1/2 signaling pathways, shows no effect on PAR2-mediated recruitment of βarrestin2 and receptor internalization.I-287 inhibits PAR2-induced secretion of IL-8 cytokine in vitro and reduces Freund's adjuvant (CFA)-induced paw edema model in mice.
Sugiol is an abietane diterpenoid, can be isolated from Calocedrus formosana bark. Sugiol has anti-inflammatory activity, could effectively reduce intracellular reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-stimulated macrophages[1].
ERK2 IN-1 is a selective ERK2 inhibitor with an IC50 of 7 nM[1].
Ulixertinib hydrochloride is a potent, orally active, highly selective, ATP-competitive and reversible covalent inhibitor of ERK1/2 kinases, with an IC50 of <0.3 nM against ERK2. Ulixertinib hydrochloride inhibits the phosphorylated ERK2 (pERK) and downstream kinase RSK (pRSK) in an A375 melanoma cell line[1][2].
TIC10 is a potent, orally active, and stable TRAIL inducer, also inhibits Akt and ERK activity.
Hydrangenol is an orally active antiphotoaging compound. It can be isolated from Hydrangea serrata leaves. Hydrangenol prevents wrinkle formation by reducing MMP and inflammatory cytokine expression and increasing moisturizing factors and antioxidant genes level[1].
Insulin Detemir is an artificial insulin, shows effect on controlling blood sugar levels. Insulin Detemir stimulates GLP-1 secretion as a consequence of enhanced Gcg expression by a mechanism involving activation of Akt- and/or extracellular signal-regulated kinase (ERK)-dependent-cat and CREB signaling pathways. Insulin Detemir can be used for type 2 diabetes research[1][2].
Aloisine A (RP107) is a a potent cyclin-dependent kinase (CDK) inhibitor with IC50s of 0.15 μM, 0.12 μM, 0.4 μM, 0.16 μM for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E, CDK5/p35, respectively. Aloisine A ininhibits GSK-3α (IC50=0.5 µM) and GSK-3β (IC50=1.5 µM). Aloisine A stimulates wild-type CFTR and mutated CFTR, with submicromolar affinity by a cAMP-independent mechanism. Aloisine A has the potential for CFTR-related diseases, including cystic fibrosis research[1][2].
CHPG 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 protects against traumatic brain injury (TBI) in vitro and in vivo by activation of the ERK and Akt signaling pathways[2].
Chicanine is a lignan compound of Schisandra chinesis, inhibits LPS-induced phosphorylation of p38 MAPK, ERK 1/2 and IκB-α, with anti-inflammatory activity[1].
EF24 is a curcumin analogue with greater anti-tumor efficacy and oral bioavailability via deactivation of the MAPK/ERK signaling pathway in oral squamous cell carcinoma (OSCC). EF24 treatment increases the levels of activated caspase 3 and 9, and decreases the phosphorylated forms of MEK1 and ERK[1][2].
DCZ19931 is a potent multi-targeting kinase inhibitor. DCZ19931 has anti-angiogenic effects on ocular neovascularization. DCZ19931 also inhibits ERK1/2-MAPK and p38-MAPK signaling[1].
Methyllinderone is an inhibitor of AP-1/STAT/ERK. Methyllinderone has anti-inflammatory effect. Methyllinderone reduce the invasion and migration rate of TPA-stimulated MCF-7 cells. Methyllinderone can be used in study breast cancer metastasis[1].
Laxiflorin B, a herbal compound, is a novel selective ERK1/2 inhibitor that has antitumor activity[1].
EVT801 is an orally active and selective inhibitor of VEGFR-3 (IC50=11 nM), which has antitumor effects. EVT801 inhibits not only VEGF-C-induced human endothelial cell proliferation, but also tumor (lymphatic) angiogenesis in tumor mouse models. EVT801 can reduce tumor hypoxia, immunosuppressive cytokines (CCL4, CCL5) and myeloid derived suppressor cells (MDSC) production. EVT801 has synergistic effect with immune checkpoint therapy (ICT), which improves ICT response rate and has better inhibitory effect on cancer mouse models[1].
Pamoic acid disodium is a potent GPR35 agonist with an EC50 value of 79 nM. Pamoic acid disodium induces GPR35 internalization and activates ERK1/2 with EC50 values of 22 nM and 65 nM, respectively. Pamoic acid disodium potently recruits β-arrestin2 to GPR35 and has an antinociceptive effect[1].
NMDAR/TRPM4-IN-2 free base (compound 8) is a potent NMDAR/TRPM4 interaction interface inhibitor. NMDAR/TRPM4-IN-2 free base shows neuroprotective activity. NMDAR/TRPM4-IN-2 free base prevents NMDA-induced cell death and mitochondrial dysfunction in hippocampal neurons, with an IC50 of 2.1 μM. NMDAR/TRPM4-IN-2 free base protects mice from MCAO-induced brain damage and NMDA-induced retinal ganglion cell loss[1].
ERK-IN-2 free base is a ERK2 inhibitor with an IC50 value of 1.8 nM. ERK-IN-2 free base might lead to off-target toxicity and/or off-target activity at dose >10 μM[1].
ERK5-IN-2 is an orally active, sub-micromolar, selective ERK5 inhibitor with IC50s of 0.82 μM, 3 μM for ERK5 and ERK5 MEF2D, respectively. ERK5-IN-2 does not interact with the BRD4 bromodomain. ERK5-IN-2 suppresses both tumor xenograft growth and basic fibroblast growth factor (bFGF) driven Matrigel plug angiogenesis[1].
Larixol is an fMLP inhibitor and also inhibits Src kinase, ERK1/2, p38 and AKT phosphorylation signals in immune regulation. Larixol can interfere with the interaction between the βγ subunit of the fMLP receptor Gi protein and its downstream molecules, thereby inhibiting fMLP-induced respiratory burst. Larixol inhibits fMLP (0.1 μM)-induced superoxide anion production (IC50: 1.98 μM), cathepsin G release (IC50: 2.76 μM), and chemotaxis. Larixol improves neutrophil hyperactivation and reduces inflammation or tissue damage. A series of Larixol derivatives were found to have inhibitory effects on FSGS-related TRPC6 functional mutants[1][2].
Ulixertinib (VRT752271) is a reversible, ATP-competitive inhibitor of ERK1 and ERK2 kinases, with IC50 of <0.3 nM against ERK2.
6-O-Isobutyrylbritannilactone is a natural melanogenesis inhibitor. 6-O-Isobutyrylbritannilactone, a sesquiterpene, can be isolated from the flowers of Inula britannica. 6-O-Isobutyrylbritannilactone inhibits IBMX (HY-12318)-induced melanin production in B16F10 cells. 6-O-Isobutyrylbritannilactone also regulates ERK, PI3K/AKT, and CREB, shows antimelanogenic activity in zebrafish embryos models[1].
(R)-VX-11e (Compound 1) is an ERK2 inhibitor[1].
Mogrol is a biometabolite of mogrosides, and acts via inhibition of the ERK1/2 and STAT3 pathways, or reducing CREB activation and activating AMPK signaling.
LM22B-10 is an activator of TrkB/TrkC neurotrophin receptor, and can induce TrkB, TrkC, AKT and ERK activation in vitro and in vivo.
SHP2-IN-23 (compound 30) is an orally active SHP2 inhibitor (IC50=38 nM) with excellent in vivo efficacy and pharmacokinetic profiles. SHP2-IN-23 inhibits ERK phosphorylation with IC50=5 nM[1].