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

ERK1/2 Inhibitor 5, a potent suppressant of the ERK1/2 pathway, is instrumental in the mitogen-activated protein kinase (MAPK) signal transduction pathway, where extracellular signal-regulated kinase (ERK) serves as a critical component of the MAPK family. This compound holds promise for the investigation or mitigation of cancer, inflammation, or various proliferative diseases[1].

ERK1/2 inhibitor 8 is a potent inhibitor of ERK that acts on ERK2 (IC50: 0.48 nM).

ERK1/2 inhibitor 7 is a potent inhibitor of ERK, acting on ERK2 (IC50: 0.94 nM).

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.

ERK1/2 Inhibitor 9 (Probe 1), a covalent antagonist of ERK1/2, exhibits sub-micromolar efficacy in cellular assays (A375 GI50=0.47 μM) and facilitates the reduction of phospho-ERK1/2 levels. When conjugated with trans-cyclo-octene (TCO) and Tz-Thalidomide (tetrazine-tagged Thalidomide), it forms the corresponding ERK-CLIPTAC, promoting targeted ERK1/2 degradation [1].

ERK1/2 Inhibitor 3, a potent inhibitor of ERK1/2, plays a crucial role in the signal transduction pathway by targeting the Mitogen-activated protein kinase (MAPK) family, specifically the extracellular signal-regulated kinase (ERK). Given its significant impact, this compound holds promise for research or prevention efforts related to cancer, inflammation, or other proliferative diseases[1].

ERK1/2 inhibitor 6 is a potent inhibitor of ERK1/2. ERK1/2 inhibitor 6 has shown potential for the study or prevention of cancer, inflammation or other proliferative diseases.

ERK1/2 inhibitor 5 is a potent inhibitor of ERK1/2. ERK1/2 inhibitor 5 has the potential to investigate or prevent cancer, inflammation or other proliferative diseases.

Fasudil (HA-1077) is a potent inhibitor of ROCK1, PKA, PKC, and MLCK.

BAY 61-3606 (Syk inhibitor IV) is a potent, ATP-competitive, reversible, and highly selective inhibitor of Syk tyrosine kinase activity (Ki= 7.5 nM), exhibiting no inhibitory effect against Btk, Fyn, Itk, Lyn, and Src.

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

LXW7 is an octamer disulfide cyclic peptide and αvβ3 integrin ligand, acts as a potent and specific endothelial progenitor cells (EPCs) and endothelial cells (ECs) targeting ligand. LXW7 is a disulfide cyclic octa-peptide (cGRGDdvc) containing unnatural amino acids flanking both sides of the main functional motif.

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

Fasudil hydrochloride (HA-1077) is a potent inhibitor of ROCK1, PKA, PKC, and MLCK with Ki of 0.33 μM, 1.0 μM, 9.3 μM and 55 μM, respectively.

Mirdametinib (PD325901) is an MEK inhibitor (IC50=0.33 nM) with selective, non-ATP-competitive, and oral activity. Mirdametinib exhibits antitumor activity by inhibiting p-ERK1/2 expression and inducing apoptosis.

Urolithin C is a gut metabolite of ellagic acid. Urolithin C induces apoptosis in PC12 cells through a mitochondria-mediated pathway.

Stattic (STAT3 Inhibitor V) is a STAT3 inhibitor (IC50=5.1 μM) that selectively inhibits STAT3 activation, dimerization, and nuclear translocation. Stattic has antitumor activity and induces apoptosis.

Ravoxertinib (GDC-0994) is an effective and orally available ERK1/2 inhibitor (IC50: 1.1/0.3 nM).

Selumetinib (AZD6244) (AZD6244) is an effective, specific inhibitor of MEK1 and ERK1/2 phosphorylation (IC50: 14/10 nM).

ROC-0929 (compound 13a) is a potent and selective inhibitor of secreted phospholipases A2 (sPLA2s), effectively targeting hGX with an IC50 of 80 nM. It efficiently inhibits the phosphorylation of ERK1/2 and p-38. sPLA2s, belonging to the disulfide-rich, Ca2+-dependent enzyme family, catalyze the hydrolysis of glycero-phospholipids at the sn-2 position, resulting in the release of a fatty acid and a lysophospholipid. ROC-0929 holds promise in researching inflammation-related diseases.

AT-533 is a potent inhibitor of Hsp90 and HSV. AT-533 blocks the HIF-1α/VEGF/VEGFR-2 signaling pathway, leading to suppress tumor growth and angiogenesis. AT-533 also inhibits the activation of the downstream pathways, including Erk1/2, FAK, Akt/mTOR/p70S6K,. AT-533 inhibits the cell migration, invasion, and the tube formation of human umbilical vein endothelial cells (HUVECs).

RWJ-56110 dihydrochloride is a potent, selective, peptide-mimetic inhibitor of PAR-1 activation and internalization (binding IC50=0.44 uM) and shows no effect on PAR-2, PAR-3, or PAR-4. RWJ-56110 dihydrochloride inhibits the aggregation of human platelets induced by both SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM), quite selective relative to U46619 . RWJ-56110 dihydrochloride blocks angiogenesis and blocks the formation of new vessels in vivo. RWJ-56110 dihydrochloride induces cell apoptosis[1][2]. Proteinase-activated receptors (PARs) are a family of G protein-coupled receptors activated by the proteolytic cleavage of their N-terminal extracellular domain, exposing a new amino terminal sequence that functions as a tethered ligand to activate the receptors.RWJ56110 inhibits the aggregation of human platelets induced by both SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM) while being quite selective relative to collagen and the thromboxane mimetic U46619 [1].RWJ-56110 dihydrochloride is fully inhibits thrombin-induced RASMC proliferation with an IC50 value of 3.5 μM. RWJ-56110 dihydrochloride shows blockade of thrombin's action with RASMC calcium mobilization (IC50=0.12 μM), as well as with HMVEC (IC50=0.13 μM) and HASMC calcium mobilization (IC50=0.17 μM)[1].RWJ56110 (0.1-10 μM; 24-96 hours) inhibits endothelial cell growth dose-dependently, with half-maximal inhibitory concentration of RWJ56110 is approximately 10 μM[2].RWJ56110 (0.1-10 μM; 6 hours) inhibits DNA synthesis of endothelial cells in a thymidine incorporation assays. Endothelial cells are in fast-growing state (50-60% confluence), RWJ56110 inhibits cell DNA synthesis in a dose-dependent manner, but when cells that are in the quiescent state (100% confluent), the inhibitory effect of PAR-1 antagonists is much less pronounced[2].RWJ56110 (0.1-10 μM; pretreatment for 15 min) inhibits thrombin-induced Erk1/2 activation in a concentration-dependent manner. However, when endothelial cells are stimulated by FBS (final concentration 4%), it reduces partially the activated levels of Erk1/2[2].RWJ56110 (30 μM; 24 hours) has an inhibitory effect on endothelial cell cycle progression. It reduces the percentage of cells in the S phase, while alterations in the percentages of G1 and G2/M cells are less pronounced[2]. Western Blot Analysis[2] Cell Line: Endothelial cells [1]. Andrade-Gordon, et al.Design, synthesis, and biological characterization of a peptide-mimetic antagonist for a tethered-ligand receptor. oc Natl Acad Sci U S A. 1999 Oct 26;96(22):12257-62. [2]. Panagiota Zania, et al. Blockade of angiogenesis by small molecule antagonists to protease-activated receptor-1: association with endothelial cell growth suppression and induction of apoptosis. J Pharmacol Exp Ther. 2006 Jul;318(1):246-54.

Larixol acts as both an fMLP inhibitor and a modulator of various signaling pathways by inhibiting Src kinase, ERK1/2, p38, and AKT phosphorylation critical for immune responses. It disrupts the interaction between the βγ subunit of the Gi protein and downstream effectors linked to the fMLP receptor, thus abrogating fMLP-induced respiratory bursts. Additionally, larixol effectively reduces fMLP (0.1 μM)-triggered superoxide anion generation (IC50: 1.98 μM), cathepsin G secretion (IC50: 2.76 μM), and cellular chemotaxis, mitigating neutrophil hyperactivation and subsequent inflammation or tissue injury. Derivatives of larixol also demonstrate inhibitory activity on TRPC6 functional mutants associated with FSGS [1] [2].

Manumycin A is an antibiotic. Manumycin A induces apoptosis and exerts antitumor activity. Manumycin A inhibits exosome biogenesis and secretion via targeted inhibition of Ras/Raf/ERK1/2 signaling. Manumycin A acts as a selective, competitive inhibitor of

LXW7 TFA, a cyclic peptide encompassing Arg-Gly-Asp (RGD), serves as an inhibitor of integrin αvβ3. It demonstrates high binding affinity towards αvβ3 integrin, evidenced by an IC50 value of 0.68 μM. Additionally, LXW7 TFA promotes the phosphorylation of VEGFR-2 and the activation of ERK1/2, contributing to its anti-inflammatory effects [1] [2] [3].

MK-8353 (SCH900353) is a potent, selective and orally available inhibitor of ERK1/2 (IC50s of 23.0 nM and 8.8 nM, respectively)

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

UNC569, the first small-molecule MER inhibitor, inhibits Mer activation and downstream signaling through ERK1/2 and AKTwith. UNC569 shows efficacy against acute lymphoblastic leukemia in vitro and in vivo.

Yoda1 is a Piezo1 ion channel agonist (EC50s = 17.1 and 26.6 μM for murine and human Piezo1-transfected HEK293T cells, respectively)

YF704 (compound 4w), a selective allosteric inhibitor of SHP2, exhibits antiproliferative effects and induces apoptosis in cancer cells with an IC50 of 0.25 μM. Furthermore, it downregulates Erk1/2 and Akt phosphorylation levels in cancer cells [1].

Ruboxistaurin is a PKC beta inhibitor. Ruboxistaurin reduces oxidative stress and attenuates left ventricular hypertrophy and dysfunction in rats with streptozotocin-induced diabetes. Ruboxistaurin attenuates diabetic nephropathy via modulation of TGF-β1/

CGP 57380 (MNK1 Inhibitor) is a potent MNK1 inhibitor with IC50 of 2.2 μM, exhibiting no inhibitory activity on p38, JNK1, ERK1 and -2, PKC, or c-Src-like kinases.

PHPS1 is an inhibitor of Shp2. PHPS1 efficiently inhibits activation of Erk1/2 by the leukemia-associated Shp2 mutant, Shp2-E76K, and blocks the anchorage-independent growth of a variety of human tumor cell lines.

Ruboxistaurin mesylate monohydrate is a PKC beta inhibitor potentially for the treatment of diabetic nephropathy and diabetic macular edema. Ruboxistaurin attenuates diabetic nephropathy via modulation of TGF-β1/Smad and GRAP pathways. Ruboxistaurin reduces oxidative stress and attenuates left ventricular hypertrophy and dysfunction in rats with streptozotocin-induced diabetes. Ruboxistaurin inhibits retinal neovascularization via suppression of phosphorylation of ERK1/2 and Akt.

Theaflavin 3,3'-digallate (8-Gingerol) , a major polyphenol found in black tea, is an inducer of oxidative stress which has anti-inflammatory and cancer chemopreventive actions, it reduces tumor angiogenesis by downregulating HIF-1αand VEGF.

KO-947 is a potent and specific inhibitor of ERK1/2 kinases.

NSC-87877 disodium (NSC87877) is a cell-permeable inhibitor of both SHP-1 and SHP-2 with IC50 values of 355 and 318 nM respectively. It also inhibits EGF-induced Erk1/2 activation in HEK293 cells and significantly reduces MDA-MB-468 cell viability/proliferation.

CNBCA, a selective and potent competitive inhibitor of the SHP2 enzyme, exhibits an IC50 value of 0.87 μM. It binds to the full-length SHP2, effectively inhibiting its enzyme activity, as well as impeding pAkt and pERK1/2. Furthermore, CNBCA suppresses the proliferation of BT474 and MDA-MB468 cells, indicating potential utility in breast cancer research [1].

Laxiflorin B, a novel selective inhibitor of ERK 1/2 derived from herbal sources, exhibits antitumor activity [1].

TAT-DEF-Elk-1 acetate is a cell-penetrating peptide inhibitor of ERK1/2 kinase phosphorylated Elk-1 with antitumor and antidepressant activity.TAT-DEF-Elk-1 acetate inhibits the phosphorylation of Elk-1, inhibits Elk-1 nuclear TAT-DEF-Elk-1 acetate inhibits Elk-1 phosphorylation and Elk-1 nuclear translocation, and can be used to study depression.

ERK1/2 inhibitor

JBJ-09-063 TFA is a mutant-selective allosteric EGFR inhibitor, displaying IC50 values of 0.147 nM for EGFR L858R, 0.063 nM for EGFR L858R/T790M, 0.083 nM for EGFR L858R/T790M/C797S, and 0.396 nM for EGFR L747S mutations. It effectively reduces phosphorylation of EGFR, Akt, and ERK1/2, demonstrating efficacy in models sensitive and resistant to EGFR tyrosine kinase inhibitors (TKI). JBJ-09-063 TFA holds potential for research in EGFR-mutant lung cancer [1].

JBJ-09-063 hydrochloride is an EGFR inhibitor selective for mutants, demonstrating IC50 values of 0.147 nM, 0.063 nM, 0.083 nM, and 0.396 nM against EGFR L858R, EGFR L858R/T790M, EGFR L858R/T790M/C797S, and EGFR L747S, respectively. It effectively inhibits EGFR, Akt, and ERK1/2 phosphorylation, showing efficacy in both EGFR tyrosine kinase inhibitor (TKI)-sensitive and -resistant models. This compound holds potential for research on EGFR-mutant lung cancer.

ITK inhibitor 6 is a selective and potent ITK inhibitor that acts on ITK (IC50: 4 nM), BTK (IC50: 133 nM), JAK3 (IC50: 320 nM), EGFR (IC50: 2360 nM), LCK (IC50: 155 nM). ITK inhibitor 6 inhibited the phosphorylation of PLCγ1 and ERK1/2 and showed anti-proliferative effect.

ADTL-EI1712 is a dual inhibitor of ERK1 and ERK5 (IC50s = 40.43 and 64.5 nM, respectively).1It reduces ERK1 and ERK5 activity by 93.5% and 89.4%, respectively, but also inhibits ERK2 activity by 92.7%, in a panel of 100 kinases at 1 μM. ADTL-EI1712 inhibits proliferation of HL-60 and MKN74, but not HeLa, cancer cells (IC50s = 1.26, 2.55, and >50 μM, respectively). It reduces tumor growth and intratumor phosphorylation of ERK1/2 and ERK5 in an MKN74 mouse xenograft model when administered at a dose of 50 mg/kg per day. 1.Wang, G., Zhao, Y., Liu, Y., et al.Discovery of a novel dual-target inhibitor of ERK1 and ERK5 that induces regulated cell death to overcome compensatory mechanism in specific tumor typesJ. Med. Chem.63(8)3976-3995(2020)

NBI-42902 is a potent inhibitor of peptide radioligand binding to the human GnRH receptor (K(i) = 0.56 nm). Tritiated NBI-42902 binds with high affinity (K(d) = 0.19 nm) to a single class of binding sites and can be displaced by a range of peptide and nonpeptide GnRH receptor ligands. In vitro experiments demonstrate that NBI-42902 is a potent functional, competitive antagonist of GnRH stimulated IP accumulation, Ca(2+) flux, and ERK1/2 activation. It did not stimulate histamine release from rat peritoneal mast cells. Finally, it is effective in lowering serum LH in castrated male macaques after oral administration. Overall, these data provide a benchmark of pharmacological characteristics required for a nonpeptide GnRH antagonist to effectively suppress gonadotropins in humans and suggest that NBI-42902 may have clinical utility as an oral agent for suppression of the hypothalamic-pituitary-gonadal axis. (source: Endocrinology. 2007 Feb;148(2):857-67. Epub 2006 Nov 9.)

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.

SB 452533 is an antagonist of the vanilloid receptor 1(pKb: 7.8).

SHR2415 is a selective, potent, orally active inhibitor of ERK1/2. SHR2415 inhibits ERK1 (IC50: 2.8 nM) and ERK2 (IC50: 5.9 nM). SHR2415 exhibits high potency in Colo205 cells (IC50: 44.6 nM). SHR2415 can be used in cancer research.