erk1

ERK1/2 inhibitor 1 is a potent, orally bioavailable compound that exhibits 60% inhibition at 1 nM and has an IC50 of 3.0 nM against ERK1 and ERK2, respectively.

ERK1/2 inhibitor 2 (ASTX029) is a selective and orally bioavailable extracellular signal-regulated kinases 1 and 2 (ERK 1/2) inhibitor, with potential antineoplastic activity.

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.

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.

AY 77 (Unk-Cha-Chg-NH2) is a potent and selective PAR2 agonist. AY 77 showed selectivity for Ca2+ and ERK1/2 signaling (ec50 value of Ca2+ release was 40 nM and ec50 value of ERK1/2 phosphorylation was 2 μM). AY 77 can promote migration of human breast cancer cells in vitro.

Notoginsenoside R1 (Sanchinoside R1) has been shown to exhibit antioxidant, antiapoptotic, anti-inflammatory, and immune-stimulatory properties.

Selumetinib (AZD6244) is a MEK1/2 inhibitor that inhibits MEK1 (IC50=14 nM) with potent selectivity and is non-ATP-competitive. Selumetinib has antitumor activity and is used for the treatment of neurofibromatosis type 1 (NF1).

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

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

Ravoxertinib hydrochloride is an orally bioavailable and selective inhibitor for ERK kinase activity (IC50: 6.1 nM and 3.1 nM for ERK1 and ERK2, respectively).

Hypothemycin is a fungal polyketide and is a multikinase inhibitor (Kis: 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).

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

Ezatiostat hydrochloride (TLK199 HCl) is an effective inhibitor of glutathione S-transferase. Ezatiostat hydrochloride is a novel glutathione analog and the potential treatment of cytopenias. In addition, Ezatiostat hydrochloride has been revealed to selectively bind to and thus inhibit GSTP1-1.

DMU-212 is a methylated derivative of resveratrol with antimitotic, anti-proliferative, antioxidant, and apoptosis-promoting activities. It induces mitotic arrest, apoptosis, and activation of ERK1/2 protein and has oral activity[1][2]. DMU-212 (0.3125-40 μM) inhibits the growth of human melanoma cells (A375, MeWo, Bro, M5)[1]. At concentrations of 30-50 μM over 24 hours, it upregulates cell cycle inhibitors, induces apoptosis, and activates ERK in A375 cells[1]. DMU-212 also induces G2/M arrest and apoptosis in cancer cells[1]. In a xenograft model of human ovarian cancer with six-week-old SCID female mice (20-24 g), DMU-212 (50 mg/kg, administered orally three times a week for 14 days) inhibits tumor growth[2]. [1]. Vasilis Pericles Androutsopoulos, et al. Activation of ERK1/2 is required for the antimitotic activity of the resveratrol analogue 3,4,5,4'-tetramethoxystilbene (DMU-212) in human melanoma cells. Exp Dermatol. 2015 Aug;24(8):632-4. [2]. Hanna Piotrowska, et al. DMU-212 inhibits tumor growth in xenograft model of human ovarian cancer. Biomed Pharmacother. 2014 May;68(4):397-400.

SUN11602, an aniline compound, mimics the neuroprotective mechanisms of basic fibroblast growth factor. It mimics the neuroprotective effects of bFGF and prevents glutamate-induced neuronal death. It also increases levels of CALB1 gene expression in cerebrocortical neurons and triggers phosphorylation of FGFR and ERK1/2.

Magnolin reduces the renal oxidative stress, suppresses caspase-3 activity, and increases Bcl-2 expression in vivo and in vitro. Magnolin has anti-inflammatory and antioxidative effects.

Astragaloside, one of the main active ingredients in Astragalus membranaceus.

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

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).

1. Cornuside (Comuside) has immunomodulatory activity . 2. Cornuside suppresses expression levels of cytokine-induced proinflammatory and adhesion molecules in the human endothelial cells. 3. Cornuside can treat myocardial I/R and protect the liver from CCl4-induced acute hepatotoxicity, by reducing oxidative stress and suppressing inflammatory responses. 4. Cornuside has anti-inflammatory activity by downregulations of iNOS and COX-2 due to NF-κB inhibition as well as the negative regulation of ERK1/2, p38, and JNK1/2 phosphorylations in RAW 264.7 cells. 5. Cornuside has protective potential against cerebral ischemic injury, may be due to the suppression of intracellular Ca(2+) elevation and caspase-3 activity, and improvements in mitochondrial energy metabolism and antioxidant properties.

Ezatiostat (TER199(free base)) is a tripeptide analog of glutathione that can selectively inhibit GSTP1-1 catalytic activity.

1. Epiberberine may be caused drug interactions based on CYP2D6 enzyme. 2. Epiberberine has anti-adipogenic effect is mediated by downregulation of the Raf/MEK1/ERK1/2 and AMPKα/Akt pathways during 3T3-L1 adipocyte differentiation. 3. Epiberberine, as the brightest FSA emitter among the alkaloids, can also serve as an efficient conformation probe for HTG DNA and discriminate the DNA G-quadruplex from the RNA counterpart.

EM127 is a highly selective and potent covalent inhibitor of SMYD3 with a KD value of 13 μM.EM127 inhibits ERK1/2 phosphorylation and inhibits transcriptional regulation of SMYD3 target genes.EM127 slowly reduces methyltransferase activity over a long period of time.EM127 has potential anticancer activity and can be used to study SMYD3 positive tumors. EM127 has potential anticancer activity and can be used to study SMYD3 positive tumors.

TAK-715 is a p38 MAPK inhibitor for p38α.