MEK

ST-168 is an orally bioavailable inhibitor of MEK and PI3K, exhibiting IC50 values of 182 nM for MEK1 and showing varying potency against PI3K isoforms with values of 69.2 nM, 41.7 nM, 1482 nM, and 2293 nM for PI3Kα, PI3Kδ, PI3Kβ, and PI3Kγ, respectively. It effectively inhibits ERK1/2 and AKT phosphorylation, inducing apoptosis in cancer cells within a 3D tumor sphere model. In vivo studies demonstrate its substantial antitumor efficacy in A375 melanoma mouse models. Additionally, ST-168 displays an improved ocular safety profile compared to conventional MEK inhibitors, evidenced by reduced caspase activation and apoptosis levels, making it a valuable tool for melanoma research.

MEK-IN-5 is a potent inhibitor of the MEK pathway, functioning by significantly decreasing the phosphorylation levels of MEK and ERK in a dose-dependent and time-dependent manner. In addition to its inhibitory effects on MEK signaling, MEK-IN-5 acts as a nitric oxide donor, contributing to its biological activity. This compound has been shown to induce apoptosis in MDA-MB-231 breast cancer cells, making it a valuable tool for research in cancer therapeutics and signaling pathways.

C16-PAF (PAF (C16)) is a phospholipid mediator and a potent platelet-activating factor that functions as a ligand for the PAF G-protein-coupled receptor (PAFR). It exhibits anti-apoptotic effects by inhibiting caspase-dependent cell death through PAFR activation. C16-PAF is a strong activator of the MAPK and MEK/ERK signaling pathways and is known to induce increased vascular permeability.

Tunlametinib is a highly selective, orally active MEK1/2 inhibitor with an IC50 of 1.9 nM against MEK1. It effectively blocks the RAS-RAF-MEK-ERK signaling cascade, inducing cell cycle arrest and apoptosis. Tunlametinib exhibits strong antiproliferative activity against RAS/RAF mutant cancer cells, including BRAF^V600E and KRAS^G12C mutants, and shows synergistic anti-tumor effects when combined with BRAF, KRAS^G12C, or SHP2 inhibitors, as well as Docetaxel. It is a promising agent for the study of targeted therapies in RAS/RAF-driven malignancies such as melanoma, colorectal cancer, and non-small cell lung cancer.

MAP855 is a highly potent, selective, ATP-competitive, and orally active MEK1/2 kinase inhibitor, with an IC50 of 3 nM for the MEK1–ERK2 cascade and a pERK EC50 of 5 nM. It exhibits equipotent inhibitory activity against both wild-type and mutant forms of MEK1/2, making it a valuable tool for MAPK pathway research.

MS432 is a first-in-class, highly selective PROTAC degrader targeting MEK1 and MEK2, based on PD0325901 and a von Hippel-Lindau (VHL) E3 ligase ligand. It demonstrates favorable plasma exposure in mice and induces MEK1 and MEK2 degradation in HT29 cells with DC₅₀ values of 31 nM and 17 nM, respectively.

RO5068760 is a potent non-ATP-competitive inhibitor of MEK1/2, demonstrating an IC50 of 0.025 μM for MEK1. This compound effectively inhibits MAPK pathway activity, leading to G1 cell cycle arrest and apoptosis, thereby reducing cancer cell proliferation. RO5068760 is applicable in research on various tumors characterized by dysregulation of the MAPK pathway, including melanoma, colorectal cancer, non-small cell lung cancer (NSCLC), and pancreatic cancer.

U0126 is a selective inhibitor of MEK1 and MEK2, functioning through a non-ATP competitive mechanism. It demonstrates potent biological activity with IC50 values of 72 nM and 58 nM for MEK1 and MEK2, respectively. U0126 is utilized in research to investigate autophagy and mitophagy processes, providing insights into cellular signaling pathways and potential therapeutic targets in cancer and other diseases.

PD-254552 is a potent inhibitor of MEK (mitogen-activated protein kinase/extracellular signal-regulated kinase kinase), playing a significant role in disrupting MAPK signaling pathways. This compound has demonstrated significant hepatotoxicity and gastrointestinal toxicity in murine models, providing valuable insights for researchers studying the side effects associated with MEK inhibition. Its properties make it a relevant candidate for investigations into cancer therapies and related pharmacological studies.

Avutometinib potassium is a potent RAF/MEK inhibitor that effectively prevents MEK phosphorylation by ARAF, BRAF, and CRAF through the formation of dominant negative RAF-MEK complexes. This compound exhibits significant anti-proliferative activity across various tumor cell lines, particularly those with KRAS mutations, including pancreatic ductal adenocarcinoma (PDAC) cell lines. In vivo studies demonstrate that Avutometinib potassium inhibits tumor growth and enhances survival in mouse models of KRAS and p53 mutant pancreatic cancer. It holds potential for research in low-grade serous ovarian carcinoma and other oncogenic conditions involving the RAF/MEK pathway.

MEK1/C-Raf-IN-1 is a selective inhibitor of MEK1 and C-Raf, exhibiting IC50 values of 97 nM and 23 nM, respectively. This compound demonstrates significant antitumor activity, making it a valuable tool for research in cancer biology and therapeutic development. Its effects on MAPK signaling pathways provide insights into potential treatment mechanisms for various malignancies.

Nedometinib is a selective MEK1 inhibitor, demonstrating an IC50 of 135 nM. By inhibiting phosphorylated ERK (p-ERK) in the MAPK signaling pathway, Nedometinib exhibits notable anticancer activity against squamous cell carcinoma. This compound is valuable for research applications related to dermatosis and neurofibromatosis.

2-Bromoaldisine is a pyrrole alkaloid that acts as a potent inhibitor of the Raf/MEK/MAPK signaling pathway. It is known to effectively suppress HIV-1 vector infection. This compound is valuable for research applications focused on cancer biology and viral pathogenesis, allowing investigators to study the effects of Raf/MEK/MAPK pathway modulation on cell proliferation and viral replication.

MEK/PI3K-IN-2 is a potent inhibitor targeting both MEK and PI3K pathways, exhibiting IC50 values of 352 nM for MEK1, 107 nM for PI3Kα, and 137 nM for PI3Kδ. This compound effectively reduces levels of phosphorylated AKT and ERK1/2, demonstrating significant anti-proliferative activity against various tumor cell lines. MEK/PI3K-IN-2 is valuable for research in cancer biology and therapeutic development aimed at disrupting these critical signaling pathways.

MEK/PI3K-IN-1 is a potent inhibitor targeting MEK and PI3K pathways, exhibiting IC50 values of 124 nM for MEK1, 130 nM for PI3Kα, and 236 nM for PI3Kδ. This compound effectively reduces levels of phosphorylated AKT (pAKT) and ERK1/2 (pERK1/2), demonstrating significant anti-proliferative effects in various tumor cell lines. MEK/PI3K-IN-1 serves as a valuable tool for research in cancer therapeutics and signaling pathway analysis.

MEK-IN-9 is a selective inhibitor of the MEK (mitogen-extracellular signal-regulated kinase) pathway. This compound has been shown to induce the expression of the tumor suppressor proteins p15 and p27, contributing to its anti-proliferative effects. MEK-IN-9 is suitable for research focusing on renal adenocarcinoma and colorectal cancer, making it a valuable tool for studying the mechanisms of tumor growth and potential therapeutic interventions.

Zapnometinib is a potent MEK inhibitor with an IC50 of 5.7 nM, acting primarily on the MAPK/ERK signaling pathway. This compound displays antiviral activity against the influenza virus and possesses antibacterial properties, making it a valuable tool for research applications in virology and microbiology. Its efficacy in inhibiting MEK highlights its potential for studies related to cancer and inflammatory diseases.

Trametiglue is a highly selective MEK inhibitor that targets both KSR-MEK and RAF-MEK pathways. It demonstrates exceptional potency through unique interfacial binding interactions, making it a valuable tool for investigating MEK-related signaling in various cancer models. Trametiglue is suitable for research applications focused on cancer biology, drug resistance mechanisms, and the development of targeted therapies.

Atebimetinib is a novel dual MEK inhibitor that targets the MEK signaling pathway, playing a critical role in cellular proliferation and survival. It demonstrates significant anti-pancreatic cancer activity, making it a valuable reagent for cancer research. This compound is suitable for studies focused on understanding MEK-related signaling mechanisms and developing targeted therapies for pancreatic and other cancers.

Luvometinib is a selective MEK inhibitor that demonstrates antitumor activity by inhibiting the MAPK/ERK signaling pathway. It is employed in research focused on cancer biology, particularly in the study of various malignancies characterized by aberrant MEK signaling. Luvometinib is valuable for investigating therapeutic strategies aimed at enhancing targeted cancer treatments.

MEK4 inhibitor-1 is a selective MEK4 inhibitor that demonstrates potent activity against pancreatic adenocarcinoma with an IC50 value of 61 nM. This compound is utilized in research to investigate the role of MEK4 signaling in cancer progression and therapeutic resistance. Its application in preclinical studies can provide insights into potential treatment strategies targeting MEK4 in various malignancies.

(2Z,3Z)-U0126 is a selective non-competitive inhibitor of MEK1 and MEK2, exhibiting potent anti-inflammatory properties with IC50 values of 72 nM for MEK1 and 58 nM for MEK2. This compound effectively inhibits anchorage-independent growth in Ki-ras-transformed rat fibroblasts by interfering with the extracellular signal-regulated kinase and mammalian target of rapamycin signaling pathways. It also has the potential to undergo isomerization and cyclization, leading to various derivatives with lower affinity for MEK and reduced inhibition of AP-1 activity compared to the original compound.

Envometinib is a dual MEK inhibitor that utilizes Deep Cyclic Inhibition (DCI) as its primary mechanism of action. It demonstrates significant antitumor activity across various in vivo models, making it a valuable tool for cancer research. Envometinib is particularly relevant for studies involving RAS and RAF mutated cancers, such as colorectal cancer and melanoma.

MEK-IN-7 is a potent, orally available, and selective inhibitor of MEK1, demonstrating an IC50 of 29.62 nM. This compound effectively inhibits the proliferation of HT29 and A375 cancer cell lines, with IC50 values of 0.62 nM and 0.40 nM, respectively. Additionally, MEK-IN-7 has been shown to suppress tumor growth in HL-29 xenograft mouse models, making it a valuable reagent for research in melanoma and colon cancer.

GW284543 hydrochloride is a selective inhibitor of MEK5, a key regulator in the MAPK signaling pathway. This compound effectively reduces phosphorylated ERK5 (pERK5) levels while decreasing the endogenous MYC protein. It is valuable for research applications investigating cellular signaling pathways, tumor biology, and potential therapeutic targets in various cancers.

MEK-IN-8 is a potent MEK inhibitor with an IC50 of less than 5 nM for phosphorylated MEK in A549 cells. This compound is valuable for investigating the MEK/ERK signaling pathway and its role in tumorigenesis. MEK-IN-8 is a useful tool for preclinical studies aimed at understanding cancer biology and potential therapeutic interventions.

MS910 is a potent and selective PROTAC degrader targeting MEK1 and MEK2 kinases. It demonstrates effective degradation of MEK1 and MEK2 in various cancer cell lines, with reported DC50 values of 118 nM for MEK1 and 55 nM for MEK2 in HT-29 cells, and 94 nM for MEK1 and 38 nM for MEK2 in SK-MEL-28 cells. MS910 is primarily utilized in cancer research to explore the therapeutic potential of targeted protein degradation.

MEK4 inhibitor-2 is a selective inhibitor targeting the MEK4 pathway, exhibiting an IC50 of 83 nM. It demonstrates significant biological activity against pancreatic adenocarcinoma, making it a valuable reagent for cancer research. This compound can be utilized in studies exploring the role of MEK4 in tumor progression and therapeutic responses.

Pimasertib hydrochloride is a selective allosteric inhibitor of MEK1/2, functioning through non-competitive inhibition of ATP-binding. This compound is notable for its ability to effectively block the MAPK signaling pathway, which is crucial in various cancers. Pimasertib is utilized in research focused on cancer therapeutics and cell signaling mechanisms, making it a valuable tool for studying tumor progression and drug resistance.

BAY-866 is an allosteric inhibitor of MEK1, exhibiting an IC50 of 14 nM. This compound effectively inhibits cell proliferation in A375 (BRAF) and HCT116 (K-Ras) cell lines, with respective IC50 values of 13 nM and 277 nM. Additionally, BAY-866 demonstrates anti-tumor activity in K-Ras-mutated A549 xenograft models, making it a valuable tool for research in cancer biology and targeted therapies.

(R)-PD 0325901CL is a selective inhibitor of mitogen-activated protein kinase kinase (MEK), a key regulator in the MAPK signaling pathway. This compound demonstrates significant antitumor activity, effectively inhibiting the proliferation of cancer cells both in vitro and in vivo. Its utility in cancer research makes it a valuable reagent for studies focused on targeted therapies and the elucidation of MEK-related mechanisms in oncogenesis.

MEK-IN-4 is a potent MEK inhibitor that specifically targets the MEK signaling pathway. It demonstrates significant biological activity in modulating cellular responses associated with inflammatory disorders and various types of cancer. This compound is an invaluable tool for research applications focused on understanding MEK-related signaling mechanisms in disease processes and therapeutic interventions.

Polfurmetinib hydrate is a potent MEK inhibitor, exhibiting an IC50 of 2 nM against A375 melanoma cells. This compound effectively hinders the MEK signaling pathway, making it a valuable tool for studies of cancer biology and therapeutic development. Its selective inhibition of MEK allows for insights into cellular signaling mechanisms and contributes to research on targeted cancer therapies.

MEK-IN-1 is a selective inhibitor of MEK (Mitogen-Activated Protein Kinase Kinase), targeting the MAPK signaling pathway. It demonstrates significant anti-proliferative effects on various cancer cell lines by blocking MEK-mediated phosphorylation of downstream ERK proteins. This compound is valuable for research applications focused on cancer biology, specifically in understanding MEK/ERK signaling and exploring therapeutic strategies for MEK-related malignancies.