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- embryos die from placental defects whereas Mek2- 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]
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MEK1 Related Products (61)
Related Products (61)
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Antibodies (3)
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Cobimetinib hemifumarate
0 ImagesSynonyms: GDC-0973 hemifumarate; XL-518 hemifumarate
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RGB-286638 free base
0 ImagesRGB-286638 free base is a potent inhibitor of CDK and MAPK9. RGB-286638 free base inhibits the activities of cyclin T1-CDK9, cyclin B1-CDK1, cyclin E-CDK2, cyclin D1-CDK4, cyclin E-CDK3 and p35-CDK5, with IC50 values of 1, 2, 3, 4, 5 and 5 nM, respectively. RGB-286638 free base inhibits GSK-3β and TAK1, with IC50 values of 3 nM and 5 nM, respectively. RGB-286638 free base induces caspase-dependent Apoptosis in cells. RGB-286638 free base delays tumor growth in an orthotopic glioblastoma mouse model. RGB-286638 free base extends survival in multiple myeloma models. RGB-286638 free base can be used in research related to glioblastoma and multiple myeloma.
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N-Feruloyloctopamine
0 ImagesSynonyms: N-trans-FeruloyloctopamineN-trans-feruloyloctopamine is a natural hydroxycinnamic acid amide compound derived from garlic outer skin, possessing tyrosinase inhibition, FGF2 inhibition, anti-melanogenic, and anti-tumor activities. N-trans-feruloyloctopamine inhibits tyrosinase activity and downregulates tyrosinase mRNA and protein expression (IC50 = 5.3 μM), and inhibits melanogenesis in α-MSH-stimulated B16F10 cells. N-trans-feruloyloctopamine inhibits Akt and p38 MAPK phosphorylation, binds to E-cadherin to block EMT, reduces Slug, inhibits hepatocellular carcinoma invasion, and induces hepatocellular carcinoma cell apoptosis. N-trans-feruloyloctopamine can be used in research related to hepatocellular carcinoma, pigmentation disorders, and UVB-induced skin damage.
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Lixisenatide acetate
0 ImagesLixisenatide acetate is a glucagon-like peptide-1 (GLP-1) receptor agonist. Lixisenatide acetate inhibits the inflammatory response through down regulation of pro-inflammatory cytokines, and suppresses of the Akt-MEK1/2 signaling pathway. Lixisenatide acetate can inhibit oxidative stress, mitochondrial dysfunction and apoptosis. Lixisenatide acetate 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.
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Cucurbitacin IIa
0 ImagesSynonyms: Hemslecin ACucurbitacin IIa (Hemslecin A) is an orally active, blood-brain barrier-permeable EGFR inhibitor with an IC50 of 1.455 nM against human EGFR. Cucurbitacin IIa induces caspase-3-dependent apoptosis, downregulates survivin expression, enhances autophagy levels, disrupts the actin cytoskeleton via actin aggregation, arrests the cell cycle at the G2/M phase, and exerts anti-inflammatory activity by inhibiting the EGFR-MAPK signaling pathway. Cucurbitacin IIa can be used in the research of inflammation-related diseases, depression, and cancers such as non-small cell lung cancer.
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Hypothemycin
0 ImagesCat. No.: HY-107417CAS No.: 76958-67-3
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Nedometinib
0 ImagesSynonyms: NFX-179Nedometinib (NFX-179) is a specific MEK1 inhibitor with an IC50 of 135 nM. Nedometinib inhibits p-ERK, MAPK. Nedometinib exerts anticancer activity against squamous cell carcinoma. Nedometinib can be used for research in dermatosis, neurofibromatosis.
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CHMFL-EGFR-202
0 ImagesCHMFL-EGFR-202 is a potent, irreversible inhibitor of epidermal growth factor receptor (EGFR) mutant kinase, with IC50s of 5.3 nM and 8.3 nM for drug-resistant mutant EGFR T790M and WT EGFR kinases, respectively. CHMFL-EGFR-202 exhibits ～10-fold selectivity for EGFR L858R/T790M against the EGFR wild-type in cells. CHMFL-EGFR-202 adopts a covalent “DFG-in-C-helix-out” inactive binding conformation with EGFR, with strong antiproliferative effects against EGFR mutant-driven nonsmall-cell lung cancer (NSCLC) cell lines.
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DS03090629
0 ImagesCat. No.: HY-164474Purity: 99.16%DS03090629 is an orally active, ATP-competitive MEK1/2 inhibitor. DS03090629 binds to the ATP-binding pocket of MEK, and this binding is unaffected by phosphorylation status. DS03090629 exhibits high affinity for both MEK and phosphorylated MEK, with Kd values of 0.11 nM and 0.15 nM, respectively. DS03090629 inhibits the MEK1F53L mutant while retaining activity relative to wild-type MEK1. DS03090629 suppresses the MAPK pathway, cell proliferation, and BRAF overexpression-mediated drug resistance in melanoma cells. DS03090629 can be used for research related to melanoma.
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MEK-IN-7
0 ImagesCat. No.: HY-177914CAS No.: 2256822-22-5MEK-IN-7 (compound WX086) is potent, orally active and selective MEK inhibitor (MEK1 IC50 = 29.62 nM). MEK-IN-7 inhibits HT29 and A375 cell proliferation with IC50s of 0.62 and 0.40 nM. MEK-IN-7 inhibits tumor growth in a HL-29 xenograft mouse model. MEK-IN-7 can be used for melanoma and colon cancer research.
