MAPK - ERK2

VRT752271 is a pyrrole inhibitors of ERK protein kinase.

TCS ERK 11e (VX-11e) is a potent and selective extracellular signal-related kinase 2 (ERK2) inhibitor (Ki values are <2, 395, 540 and 852 nM for ERK2, GSK-3, Aurora Kinase A and Cdk2 respectively). Potently blocks proliferation of HT29 cells (IC50 = 48 nM).

GDC-0994 is a potent and selective Erk1/2 inhibitor. GDC-0994 inhibits both ERK phosphorylation and activation of ERK-mediated signal transduction pathways.

CC-90003 is an irreversible inhibitor of ERK1/2 with IC50s in the 10-20 nM range and shows good kinase selectivity in a 258-kinase biochemical assay.

AG-126 is a ERK2 inhibitor that selectively inhibits the phosphorylation of ERK1 (p44) and ERK2 (p42) at 25-50 μM.

Rineterkib (ERK-IN-1) (compound B) is a RAF and ERK1/2 inhibitor in the treatment of a proliferative disease characterized by activating mutations in the MAPK pathway.

ERK2 IN-1 is a selective ERK2 inhibitor with an IC50 of 7 nM.

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.

KO-947 is a potent and selective inhibitor of ERK1/2 kinases with potential clinical utility in MAPK pathway dysregulated tumors.

Cafestol is an orally active diterpenoid and an inhibitor of ERK2. It exhibits multiple biological activities, including elevation of blood lipids, anti-inflammatory, anti-angiogenic, and anti-diabetic effects. Additionally, cafestol induces apoptosis and autophagy in tumor cells, making it a potential candidate for cancer research.

SHR2415 is a highly potent, selective, and orally active ERK1/2 inhibitor with IC50 values of 2.8 nM for ERK1 and 5.9 nM for ERK2. It demonstrates strong antiproliferative activity in Colo205 cells with an IC50 of 44.6 nM. SHR2415 is a promising compound for cancer research, particularly in targeting the MAPK/ERK signaling pathway.

ASN007 (ERK-IN-3) benzenesulfonate is a potent, orally active ERK1/2 inhibitor with low single-digit nanomolar IC50 values. It is under investigation for the treatment of cancers driven by RAS mutations.

ERK1/2 Inhibitor 7 is a highly potent ERK inhibitor, exhibiting an IC50 of 0.94 nM against ERK2. It is referenced in patent WO2021110168A1 (compound WX006).

Rineterkib hydrochloride (compound B) is an orally bioavailable inhibitor of ERK1 and ERK2, developed for the treatment of proliferative diseases driven by activating mutations in the MAPK signaling pathway. It exhibits potent antitumor activity, particularly in cancers harboring KRAS or BRAF mutations.

ASN007 (also known as ERK-IN-3) is a potent, orally active inhibitor of extracellular signal-regulated kinases ERK1 and ERK2, exhibiting low single-digit nanomolar IC₅₀ values. By directly targeting ERK, ASN007 effectively disrupts the MAPK/ERK signaling pathway, which is frequently activated in RAS-mutant cancers. It serves as a valuable therapeutic candidate and research tool for studying and potentially treating malignancies driven by aberrant RAS signaling, including colorectal, pancreatic, and non-small cell lung cancers.

mSIRK (G-Protein βγ Binding Peptide) is a cell-permeable peptide that functions as an activator of ERK1/2 signaling, with an EC₅₀ of 2.5–5 μM. It disrupts the interaction between the G-protein α and βγ subunits, promoting dissociation of the α subunit independently of nucleotide exchange. By modulating G-protein signaling, mSIRK enables selective activation of downstream pathways, such as ERK1/2, and serves as a valuable tool for studying G-protein–mediated signal transduction and ERK pathway activation.

ASTX029 (Example 1) is a highly potent dual inhibitor of ERK1 and ERK2, with an IC₅₀ of 2.7 nM. By directly targeting both isoforms of extracellular signal-regulated kinase, ASTX029 effectively blocks downstream MAPK/ERK signaling, a pathway frequently dysregulated in cancer. It exhibits strong anticancer activity and is being investigated as a therapeutic candidate for malignancies driven by aberrant RAS-RAF-MEK-ERK signaling.

Methyl helicterate is a triterpenoid compound that functions as an inhibitor of the ERK1/2 signaling pathway. It demonstrates significant biological activity by inhibiting hepatic stellate cell activation and promoting apoptosis in these cells. This manipulation of the ERK1/2 pathway positions methyl helicterate as a valuable reagent for research focused on liver fibrosis and related conditions.

ERK1/2 inhibitor 13 is a potent dual inhibitor of ERK1 and ERK2, exhibiting IC50 values of 91.71 nM and 97.87 nM, respectively. This compound demonstrates significant activity in inhibiting the proliferation of tumor cell lines, including MCF-7, 4T1, MDA-MB-468, and HCC1970, with IC50 values ranging from 0.67 to 2.76 μM. Additionally, ERK1/2 inhibitor 13 effectually inhibits cancer cell migration and induces apoptosis and autophagy in MCF-7 cells, while also displaying antitumor and anti-metastatic properties in a 4T1 xenograft mouse model, making it a valuable reagent for cancer research applications.

SF-3-030 is a selective, non-ATP competitive inhibitor of ERK1/2, targeting the MAPK signaling pathway. It has demonstrated the ability to induce apoptosis specifically in melanoma cells with mutated BRAF and activated ERK1/2 signaling. Additionally, SF-3-030 has shown potential in alleviating several characteristics of asthma in murine models, making it valuable for research focused on both melanoma and asthma pathophysiology.

(R)-VX-11e is a selective inhibitor of the extracellular signal-regulated kinase 2 (ERK2), a key component of the MAPK signaling pathway. This compound has been shown to effectively interfere with ERK2-mediated signal transduction, leading to alterations in cell proliferation and differentiation. It serves as a valuable tool in cancer research by elucidating the role of ERK2 in tumor progression and therapeutic response.

ERK-IN-2 is a potent ERK2 inhibitor with an IC50 of 1.8 nM, demonstrating strong selectivity for its target. This compound effectively modulates ERK2 activity, which is critical in various signaling pathways related to cell growth, proliferation, and survival. ERK-IN-2 is well-suited for research applications investigating ERK signaling in cancer and other diseases, though caution is advised regarding potential off-target effects at doses exceeding 10 μM.

ERK1/2 Inhibitor 3 is a selective inhibitor of ERK1/2, members of the mitogen-activated protein kinase (MAPK) family, which are critical components in cellular signal transduction pathways. This compound demonstrates significant potential in the study of cancer, inflammation, and other proliferative diseases due to its ability to modulate ERK signaling. Research applications include elucidating the role of ERK1/2 in various pathological conditions and exploring therapeutic strategies targeting aberrant MAPK activity.

MK-8353 hydrochloride is a selective inhibitor of ERK1/2, demonstrating IC50 values of 23.0 nM and 8.8 nM for each target, respectively. This compound shows significant antitumor activity, making it a valuable tool for cancer research. Its oral bioavailability allows for convenient administration in preclinical studies focused on the MAPK signaling pathway and its role in tumor progression.

TAT-MEK1 is an ERK2 inhibitor that combines the TAT peptide with the N-terminal region of MEK1, enabling efficient cellular uptake. This compound exhibits an in vitro IC50 of 29 μM for ERK2, demonstrating its potent inhibitory action. TAT-MEK1 is primarily utilized in research to investigate ERK2-related signaling pathways and explore its implications in various cellular processes and disease states.

ERK2/p38α MAPK-IN-1 is a selective inhibitor targeting ERK2 and p38α MAPK, exhibiting an IC50 of 82 μM for ERK2. This compound binds allosterically to both ERK2 and p38α MAPK, influencing their activity through distinct mechanisms. It is primarily utilized in research concerning type 2 diabetes, contributing to studies aimed at understanding the molecular pathways involved in this condition.

ERK1/2 Inhibitor 4 is a selective inhibitor targeting the extracellular signal-regulated kinases 1 and 2 (ERK1/2), key components of the mitogen-activated protein kinase (MAPK) signaling pathway. This compound exhibits potent inhibition of ERK1/2 activity, making it a valuable tool for studying cellular signaling and its implications in cancer, inflammatory responses, and various proliferative disorders. Research applications include elucidating the role of ERK1/2 in tumorigenesis and exploring therapeutic strategies in related diseases.

STE-MEK1(13) is a selective inhibitor of the ERK1/2 pathway, effectively blocking the phosphorylation of both ERK1 and ERK2. With an IC50 range of 13-30 μM, this cell-permeable compound is valuable for investigating the role of ERK signaling in cellular processes. Applications include studies on cancer biology, cell proliferation, and differentiation, making it a useful tool for researchers exploring MAPK pathway modulation.

ERK-IN-2 free base is a selective inhibitor of ERK2, demonstrating an IC50 value of 1.8 nM. This compound is useful for studying the role of ERK2 in various signaling pathways and cellular processes. Researchers should be mindful of potential off-target toxicity or activity at concentrations exceeding 10 μM, which may impact experimental outcomes.

ERK2-IN-3 is a selective inhibitor of ERK2, effectively blocking the phosphorylation of both Erk2WT and Erk2DS1 activation loops with IC50 values of 5 μM and 42 nM, respectively. This compound provides valuable insights into the role of ERK2 in various signaling pathways and is applicable in research related to cancer, cell proliferation, and differentiation. ERK2-IN-3 may facilitate the study of ERK signaling and its potential therapeutic interventions.

ERK1/2 Inhibitor 5 is a highly effective inhibitor specifically targeting ERK1/2, members of the mitogen-activated protein kinase (MAPK) family. By interfering with the MAPK signaling pathway, this compound demonstrates significant potential in research applications related to cancer, inflammation, and other proliferative disorders. Its ability to modulate cellular signaling makes it a valuable tool in the study of various pathophysiological conditions.

β-Neo-Endorphin acetate is an endogenous opioid peptide that primarily acts as an Erk1/2 activator. Originating from porcine hypothalamus as a precursor to Leu-enkephalin, it demonstrates significant biological activity by activating Erk1/2, as well as matrix metalloproteinases MMP-2 and MMP-9. This compound is valuable for research focused on neurobiology, pain modulation, and cellular signaling pathways involving opioid receptors.

ERK2 allosteric-IN-1 is a selective allosteric inhibitor of ERK2, exhibiting an IC50 value of 11 μM. This compound modulates ERK2 activity, providing a valuable tool for investigating the role of ERK1/2 signaling in various biological processes. Its specificity for ERK2 makes it suitable for studies in cancer research, cellular signaling, and related therapeutic applications.

OP-1118 is a potent dual inhibitor of NF-κB and ERK1/2, targeting critical signaling pathways involved in inflammation and cell survival. This compound demonstrates significant anti-inflammatory, cytoprotective, anti-apoptotic, and antibacterial activities by inhibiting the phosphorylation of NF-κB and ERK1/2, leading to a reduction in pro-inflammatory cytokine expression. In preclinical models of Clostridium difficile infection, OP-1118 effectively mitigates toxin-induced intestinal inflammation, cellular damage, and apoptosis, with its protective effects possibly reversible by PMA. This makes OP-1118 a valuable reagent for research into inflammatory conditions and therapeutic interventions.

ERK1/2 inhibitor 6 is a selective inhibitor targeting extracellular signal-regulated kinases 1 and 2 (ERK1/2), key components of the mitogen-activated protein kinase (MAPK) signaling pathway. This compound exhibits significant activity in modulating signal transduction processes, making it a valuable tool in cancer research, inflammation studies, and the investigation of other proliferative diseases. Its potential applications include elucidating the role of ERK1/2 in cellular processes and exploring therapeutic strategies for related pathologies.

ERK1/2 inhibitor 10 is a highly potent inhibitor of ERK1 and ERK2, exhibiting IC50 values of 0.11 nM and 0.08 nM, respectively. This compound effectively blocks the phosphorylation of downstream substrates, including p90RSK and c-Myc, leading to enhanced cell apoptosis and incomplete autophagy-related cell death. ERK1/2 inhibitor 10 demonstrates significant antitumor activity against triple-negative breast cancer and colorectal cancer models, particularly those with BRAF and RAS mutations, making it a valuable tool for cancer research.

ERK1/2 Inhibitor 12 is a selective inhibitor of the ERK1 and ERK2 signaling pathways. It effectively inhibits ERK-mediated phosphorylation of caspase-9 and p90Rsk-1 kinase, demonstrating significant anti-cancer activity. This compound is suitable for research applications focused on cancer biology and the modulation of ERK signaling in various cellular contexts.

ETP-45835 dihydrochloride is a selective inhibitor of Erk2, exhibiting an IC50 value of 18.7 μM. This compound demonstrates significant inhibitory effects on cell proliferation, with an EC50 value of 0.9 μM. ETP-45835 is valuable for research applications focused on cell signaling pathways and the modulation of Erk2 activity in various biological contexts.

Tizaterkib (hexanedioic acid) is a potent and selective inhibitor of ERK2, exhibiting an IC50 of 0.6 nM. This compound effectively disrupts ERK2 signaling pathways, making it valuable for investigating the role of ERK2 in various biological processes. Its application extends to cancer research and drug discovery, providing insights into therapeutic strategies targeting ERK2-associated pathways.

Fulipiftide is a short peptide that acts as an activator of the ERK2 and STAT3 signaling pathways. This compound promotes the expansion of nuclear stem cell factor +TSPC, demonstrating significant anti-inflammatory activity. Fulipiftide is particularly useful in research related to acute tendon injury and in studies exploring regenerative medicine and tissue repair mechanisms.

Ulixertinib hydrochloride is a potent, orally active inhibitor of the ERK1/2 kinases, functioning primarily through ATP competition and reversible covalent binding. With an IC50 of less than 0.3 nM against ERK2, this compound effectively inhibits phosphorylated ERK2 (pERK) and its downstream target, RSK (pRSK) in A375 melanoma cells. Ulixertinib hydrochloride is valuable for research aimed at understanding the role of ERK signaling in cancer biology and therapeutic strategies targeting this pathway.

ERK1/2 Inhibitor 9 is a covalent inhibitor targeting ERK1/2, exhibiting sub-micromolar activity in cellular assays with a GI50 of 0.47 μM in A375 cells. This compound effectively downregulates phospho-ERK1/2 levels, thereby impacting downstream signaling pathways. Additionally, ERK1/2 Inhibitor 9 is functionalized with trans-cyclo-octene (TCO) and Tz-Thalidomide, enabling the formation of ERK-CLIPTAC for targeted degradation of ERK1/2. This makes it a valuable tool for research into cancer signaling mechanisms and targeted protein degradation strategies.

ERK2-IN-4 is a selective inhibitor of the ERK2 pathway, demonstrating a Ki of 0.006 μM. This compound effectively disrupts ERK signaling, making it a valuable tool in cancer research. Its specificity and potency allow for detailed studies of ERK2's role in tumorigenesis and related signaling pathways.