MEK2

MEK2 (mitogen-activated protein kinase kinase 2) is a dual-specificity kinase that activates ERK1/2, regulating DNA repair, proliferation, and differentiation in mammalian cells^[1]^[2]. Mechanistically, MEK2 interacts with the ribonucleotide reductase subunit p53R2, enhancing RNR activity under serum stimulation and after ionizing radiation, which supports nucleotide supply for DNA synthesis and repair^[2]. Compared with MEK1, MEK2 can be sufficient for the proliferation of specific cancer cells, such as SK-MEL-28 melanoma cells, even when MEK1 activity is inhibited, indicating isoform-specific control of ERK-mediated proliferation^[3]. In disease models, MEK2 knockdown selectively reduces invasive capacity in pancreatic cancer cells, highlighting its distinct contribution to tumor progression^[4]. Inhibition of MEK2 also modulates TREM2 cell surface recruitment in microglia, linking MEK2 signaling to potential neuroinflammatory processes^[5]. Pharmacological inhibitors targeting MEK2, either alone or in combination with MEK1 inhibitors, are being utilized in experimental applications for cancer and inflammatory models, demonstrating the utility of isoform-selective modulation^[6]^[7]^[8]. Overall, MEK2 functions as a key regulator within the ERK/MAPK cascade, with specific roles in DNA repair, cellular proliferation, tumor invasiveness, and immune modulation, distinct from the overlapping but non-redundant activities of MEK1^[4]^[2]^[3]^[7].

References:

[1]. Werner U, et al. Die Vorbereitung hyperthyreoter Patienten auf die Operation [Preparation of hyperthyreotic patients for surgery]. Z Arztl Fortbild (Jena). 1975 May 15;69(10):531-5. German.

[2]. Mukherjee T, et al. Exploring Small-Molecule Inhibitors Targeting MAPK Pathway Components: Focus on ERK, MEK1, and MEK2 Kinases in Cancer Treatment. Chemical Biology Letters. 2024;11(2):659.

[3]. Schapansky J, et al. MEK1/2 activity modulates TREM2 cell surface recruitment. J Biol Chem. 2021 Jan-Jun;296:100218.

[4]. Bélanger LF, et al. Mek2 is dispensable for mouse growth and development. Mol Cell Biol. 2003 Jul;23(14):4778-87.

[5]. Piao C, et al. MEK2 regulates ribonucleotide reductase activity through functional interaction with ribonucleotide reductase small subunit p53R2. Cell Cycle. 2012 Sep 1;11(17):3237-49.

[6]. Lee CS, et al. MEK2 is sufficient but not necessary for proliferation and anchorage-independent growth of SK-MEL-28 melanoma cells. PLoS One. 2011 Feb 18;6(2):e17165.

[7]. Diamond EL, et al. Efficacy of MEK inhibition in patients with histiocytic neoplasms. Nature. 2019 Mar;567(7749):521-524.

[8]. Long ME, et al. MEK1/2 Inhibition Promotes Macrophage Reparative Properties. J Immunol. 2017 Jan 15;198(2):862-872.

MEK2 Inhibitors (25)

MEK2 Related Products (27):

By Type:	Pan (17) Selective (3)

Cat. No.	Product Name	Effect	Purity

HY-10999

Trametinib	Inhibitor	99.93%
Trametinib (GSK1120212; JTP-74057) is an orally active MEK inhibitor that inhibits MEK1 and MEK2 with IC₅₀s of about 2 nM. Trametinib activates autophagy and induces apoptosis, cross the blood-brain barrier (BBB), used in research related to subarachnoid hemorrhage (SAH).

HY-10254

Mirdametinib	Inhibitor	99.95%
Mirdametinib (PD0325901) is an orally active, selective and non-ATP-competitive MEK inhibitor with an IC₅₀ of 0.33 nM. Mirdametinib exhibits a K_i^app of 1 nM against activated MEK1 and MEK2. Mirdametinib suppresses the expression of p-ERK1/2 and induces apoptosis. Mirdametinib has anti-cancer activity for a broad spectrum of human tumor xenografts.

HY-12031A

U0126	Inhibitor	98.57%
U0126 is a potent, non-ATP competitive and selective MEK1 and MEK2 inhibitor, with IC₅₀s of 72 nM and 58 nM, respectively. U0126 is an autophagy and mitophagy inhibitor.

HY-12028

PD98059	Inhibitor	99.94%
PD98059 is a potent and selective MEK inhibitor with an IC₅₀ of 5 µM. PD98059 binds to the inactive form of MEK, thereby preventing the activation of MEK1 (IC₅₀ of 2-7 µM) and MEK2 (IC₅₀ of 50 µM) by upstream kinases. PD98059 is a ERK1/2 signaling inhibitor. PD98059 is a ligand for the aryl hydrocarbon receptor (AHR), and suppresses TCDD binding (IC₅₀ of 4 μM) and AHR transformation (IC₅₀ of 1 μM). PD98059 also inhibits Mycobacterium bovis Bacillus CalmetteGuerin (BCG)-induced autophagy.

HY-50706

Selumetinib	Inhibitor	99.72%
Selumetinib (AZD6244) is selective, non-ATP-competitive oral MEK1/2 inhibitor, with an IC₅₀ of 14 nM for MEK1. Selumetinib (AZD6244) inhibits ERK1/2 phosphorylation. Selumetinib can penetrate the blood brain barrier (BBB).

HY-181978

GIT1-IN-1	Inhibitor
GIT1-IN-1 is an inhibitor of ARF GTPase-activating protein 1 (GIT1) with a K_D of 6.2 μM. GIT1-IN-1 induces apoptosis (apoptosis) in liver and colon cancer cells, arrests the cell cycle at the G2/M phase, and inhibits cell proliferation, colony formation and migration. GIT1-IN-1 inhibits the activities of MEK and ERK, reduces the expression level of cyclin D1, and stabilizes cyclin B1 protein in liver and colon cancer cells. GIT1-IN-1 can be used in the research of liver cancer and colon cancer.

HY-180327

NEPP11
NEPP11 is a cyclopentenone prostaglandin analogue. NEPP11 can inhibit glutamate-induced HT22 cell death in mouse hippocampus and prevent manganese-induced apoptosis in PC12 cells. NEPP11 can activate Nrf2 and maintain MEK1/2 and ERK1/2 activity by inhibiting c-Raf downregulation. NEPP11 exerts a neuroprotective effect in a mouse model of focal cerebral ischemia caused by permanent middle cerebral artery occlusion.

HY-12031

U0126-EtOH	Inhibitor	99.41%
U0126 (U0126-EtOH) is a potent, non-ATP competitive and selective MEK1 and MEK2 inhibitor, with IC₅₀s of 72 nM and 58 nM, respectively. U0126 is an autophagy and mitophagy inhibitor.

HY-10999A

Trametinib (DMSO solvate)	Inhibitor	99.50%
Trametinib (DMSO solvate) (GSK-1120212 (DMSO solvate)) is an orally active MEK inhibitor that inhibits MEK1 and MEK2 with IC₅₀s of about 2 nM. Trametinib (DMSO solvate) activates autophagy and induces apoptosis. This product is in solid form, a DMSO solvate, and a stable crystalline form.

HY-P0119

Lixisenatide	Inhibitor	99.93%
Lixisenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist. Lixisenatide inhibits the inflammatory response through down regulation of pro-inflammatory cytokines, and suppresses of the Akt-MEK1/2 signaling pathway. Lixisenatide can inhibit oxidative stress, mitochondrial dysfunction and apoptosis. Lixisenatide can be used for the researches of inflammation, metabolic disease, neurological disease and cardiovascular disease, such as rheumatoid arthritis, diabetes, Alzheimer's disease and atherosclerosis.

HY-402361

TERT activator-1		99.91%
TERT activator-1 is a small molecule activator of telomerase reverse transcriptase (TERT). TERT activator-1 promotes TERT transcription through the MEK/ERK/AP-1 signaling cascade. TERT activator-1 promotes adult neurogenesis and enhances neuromuscular function. TERT activator-1 reduces cellular senescence and systemic inflammation in aged mice, and can be used in the study of aging.

HY-132844

Tunlametinib	Inhibitor	99.53%
Tunlametinib is a highly selective, orally active MEK1/2 inhibitor (IC₅₀=1.9 nM, MEK1). Tunlametinib blocks the RAS-RAF-MEK-ERK signaling pathway, arrests tumor cell cycle and promotes apoptosis. Tunlametinib potently inhibits the proliferation of RAS/RAF mutant cancer cells (such as BRAF V600E, KRAS G12C mutant cells). Tunlametinib shows synergistic anti-tumor effects with BRAF/KRASG12C/SHP2 inhibitors, Docetaxel (HY-B0011). Tunlametinib can be used to study targeted therapy for RAS/RAF mutation-driven malignancies (such as melanoma, colorectal cancer, and non-small cell lung cancer).

HY-12042

Pimasertib	Inhibitor	99.60%
Pimasertib (AS703026) is a highly selective, ATP non-competitive allosteric orally available MEK1/2 inhibitor.

HY-153181

Trametiglue	Inhibitor	98.81%
Trametiglue, a derivative of Trametinib (HY-10999), targets both KSR-MEK and RAF-MEK with unprecedented potency and selectivity via unique interfacial binding interactions.

HY-14691

Refametinib	Inhibitor	99.82%
Refametinib (BAY 869766; RDEA119) is an orally available, potent, non-ATP-competitive, selective, allosteric MEK1/MEK2 inhibitor with IC₅₀s of 19 nM and 47 nM, respectively.

HY-B0023

Azelnidipine	Inhibitor	99.79%
Azelnidipine (CS 905) is a dihydropyridine calcium channel blocker that is effective orally. Azelnidipine inhibits the intracellular calcium ion flow and lower blood pressure by selectively blocking L-type calcium channel on the membrane of vascular smooth muscle. Azelnidipine inhibits esophageal squamous cell carcinoma proliferation by targeting MEK1/2. Azelnidipine also has anti-inflammatory, antioxidant and neuroprotective effects .

HY-12058

AZD8330	Inhibitor	99.06%
AZD8330 (ARRY-424704) is a potent, uncompetitive MEK1/MEK2 inhibitor, with an IC₅₀ of 7 nM.

HY-15437

SL327	Inhibitor	99.57%
SL327 inhibits MEK1 and MEK2, with IC₅₀ values of 180 nM and 220 nM, respectively.

HY-130602

MS432	Inhibitor	99.72%
MS432 is a first-in-class and highly selective PD0325901-based von Hippel-Lindau-recruiting PROTAC degrader for MEK1 and MEK2. MS432 displays good plasma exposure in mice, exhibiting DC₅₀ values of 31 nM and 17 nM for MEK1, MEK2 in HT29 cells respectively.

HY-12062

PD318088	Inhibitor	99.82%
PD318088 is a potent, allosteric and non-ATP competitive MEK1/2 inhibitor, an analog of PD184352 (HY-50295). PD318088 binds simultaneously with ATP in a region of the MEK1 active site that is adjacent to the ATP-binding site. PD318088 can be used for cancer research.

Name
Email *

	Sorry, but the email address you supplied was invalid.