MEK1

MEK1 is a MAP kinase or ERK kinase that phosphorylates the ERK gene product and acts as an immediate upstream activator of ERK signaling^[1]^[2]. Mechanistically, MEK1 and MEK2 phosphorylate and activate ERK1/ERK2, positioning MEK proteins as pathway gatekeepers in the RAS-RAF-MEK-ERK cascade^[3]^[4]. This cascade regulates cell proliferation, differentiation, survival, invasion, and other ERK-dependent cellular responses^[3]^[5]. In disease models, ERK pathway activation is prominent in cancers driven by receptor tyrosine kinase, RAS, BRAF, CRAF, MEK1, or MEK2 alterations, which promote growth factor-independent ERK1/2 activation^[5]. Compared with MEK2, MEK1 shares the same ERK substrates, but Mek1-null embryos die from placental defects whereas Mek2-null mice survive, indicating isoform-related developmental differences and functional redundancy controlled by total MEK protein level^[4]. Structurally, MEK1 and MEK2 are closely related dual-specificity tyrosine/threonine kinases with a hydrophobic allosteric pocket adjacent to the ATP-binding site^[6]^[5]. For experimental applications, PD098059 selectively inhibited MEK without significant inhibition of MAPK itself, and allosteric MEK blockade suppressed colon tumor growth in vivo^[7]^[8].

References:

[1]. Crews CM, et al. The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product. Science. 1992 Oct 16;258(5081):478-80. [Content Brief]

[2]. Zheng CF, et al. Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases. J Biol Chem. 1993 Nov 15;268(32):23933-9. [Content Brief]

[3]. Shaul YD, et al. The MEK/ERK cascade: from signaling specificity to diverse functions. Biochim Biophys Acta. 2007 Aug;1773(8):1213-26. [Content Brief]

[4]. Aoidi R, et al. Functional redundancy of the kinases MEK1 and MEK2: Rescue of the Mek1 mutant phenotype by Mek2 knock-in reveals a protein threshold effect. Sci Signal. 2016 Jan 26;9(412):ra9. [Content Brief]

[5]. Caunt CJ, et al. MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road. Nat Rev Cancer. 2015 Oct;15(10):577-92. [Content Brief]

[6]. Ohren JF, et al. Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition. Nat Struct Mol Biol. 2004 Dec;11(12):1192-7. [Content Brief]

[7]. Dudley DT, et al. A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7686-9. [Content Brief]

[8]. Sebolt-Leopold JS, et al. Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Nat Med. 1999 Jul;5(7):810-6. [Content Brief]

MEK1 Related Products (57)
Antibodies (3)

MEK1 Related Products (57):

By Type:	Pan (18) Selective (18)
By Effects:	Inhibitors (50) Antagonists (2) Degraders (2) Ligand (1)

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-175585

MEK1 ligand-1	Ligand
MEK1 ligand-1 is a MEK1 ligand. MEK1 ligand-1 serves as a ligand for the target protein in the design and development of PROTAC MEK1 degraders, such as PROTAC MEK1 Degrader-1 (HY-153864).

HY-184145

AKT1-IN-13	Inhibitor
AKT1-IN-13 is an orally active AKT1 inhibitor with an IC₅₀ of 5.17 μM. AKT1-IN-13 also exhibits high inhibitory activity against PAK1, PKA, MAP2K1 (MEK1 / MAPKK1) and MAPK1 (ERK2). AKT1-IN-13 induces cell apoptosis, activates the pro-apoptotic protein BAX, inhibits the anti-apoptotic protein Bcl-2, and activates caspase 3 simultaneously. As a cytotoxic agent, AKT1-IN-13 exerts a killing effect on orthotopically transplanted liver cancer in an AKT1-dependent manner. AKT1-IN-13 can be used in studies related to hepatocellular carcinoma.

HY-185446

KZ-02	Inhibitor
KZ-02 is an orally active dual MEK1/Pim-1 kinase inhibitor, with an IC₅₀ of 1.07 nM against MEK1 and an IC₅₀ of 1.34 μM against Pim-1. KZ-02 reduces the phosphorylation levels of ERK and Cdc25C, and promotes the proteasomal degradation of Pim-1 protein. KZ-02 inhibits cancer cell growth and exerts anti-tumor effects. KZ-02 can be used in the research of colorectal cancer.

HY-13064

Cobimetinib	Inhibitor	99.81%
Cobimetinib (GDC-0973, RG7420) is a potent, selective and oral MEK1 inhibitor with an IC₅₀ of 4.2 nM for MEK1.

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-N0776

Isorhamnetin	Inhibitor	99.94%
Isorhamnetin is a flavonoid compound extracted from the Chinese herb Hippophae rhamnoides L.. Isorhamnetin suppresses skin cancer through direct inhibition of MEK1 and PI3K.

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-50295

CI-1040	Inhibitor	99.91%
CI-1040 (PD 184352) is an orally active, highly specific, small-molecule inhibitor of MEK with an IC₅₀ of 17 nM for MEK1.

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-15610

GDC-0623	Inhibitor	98.74%
GDC-0623 (RG 7421) is a potent, ATP-uncompetitive inhibitor of MEK1 (K_i=0.13 nM, +ATP), and displays 6-fold weaker potency against HCT116 (KRAS (G13D), EC₅₀=42 nM) versus A375 (BRAF^V600E, EC₅₀=7 nM).

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.

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MEK1

MEK1 Related Products (57)

Antibodies (3)

MEK1 Related Products (57):