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 (62)
Related Products (62)
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Antibodies (3)
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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.
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RO5068760
0 ImagesCat. No.: HY-111033CAS No.: 947182-25-4RO5068760 is a potent, orally active and selective non-ATP-competitive MEK1/2 inhibitor with an IC50 of 0.025 μM for MEK1. RO5068760 significantly inhibits MAPK pathway activity, thereby inducing G1 cell cycle arrest and apoptosis to inhibit cancer cell growth. RO5068760 exhibits significant efficacy in a broad spectrum of tumors with aberrant MAPK pathway activation. RO5068760 can be used for melanoma, colorectal cancer, non-small cell lung cancer (NSCLC), and pancreatic cancer research.
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AKT1-IN-13
0 ImagesCat. No.: HY-184145AKT1-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.
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MEK/RAF-IN-1
0 ImagesCat. No.: HY-162873MEK/RAF-IN-1 (Compound 16b) is an inhibitor of both MEK and RAF. It shows potent inhibition with IC50 values of 28 nM for MEK1, and 3 nM each for BRAF and BRAFV600E. MEK/RAF-IN-1 demonstrates significant antitumor activity, effectively inhibiting cell proliferation in vitro against MIA PaCa-2 (G12C KRAS), HCT116 (G13D KRAS), and C26 (G12D KRAS) cells. Additionally, it inhibits tumor growth in xenograft mouse models of colorectal cancer.
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MS910
0 ImagesCat. No.: HY-170982CAS No.: 2756323-28-9MS910 is a CRBN-recruiting MEK1/2 PROTAC degrader, with a DC50 of 94 nM against MEK1 and 38 nM against MEK2 in SK-MEL-28 cells. MS910 induces the degradation of GSPT1, IKZF1/3 and ZFP91, thereby inhibiting the downstream ERK signaling pathway and cancer cell growth. MS910 is applicable to research related to colorectal cancer and melanoma.
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MEK/PI3K-IN-2
0 ImagesCat. No.: HY-144693CAS No.: 2281803-33-4
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KZ-02
0 ImagesCat. No.: HY-185446CAS No.: 1801756-14-8KZ-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.
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MEK/PI3K-IN-1
0 ImagesCat. No.: HY-144692CAS No.: 2281803-28-7
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MEK-IN-10
0 ImagesCat. No.: HY-183674CAS No.: 3096958-11-8MEK-IN-10 is an orally active pan-MEK/RAF non-degrading molecular glue with an IC50 of 782 nM against human MEK1. MEK-IN-10 blocks the phosphorylation of MEK and ERK, induces and stabilizes the MEK1-RAF complex, and disrupts the RAS-MAPK signaling pathway. MEK-IN-10 induces apoptosis in cancer cells and arrests cells at the G0/G1 phase. MEK-IN-10 induces tumor growth inhibition in mouse xenograft models. MEK-IN-10 can be used in the research of RAS-driven cancers, such as colorectal cancer and pancreatic cancer.
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(E/Z)-Chk2-IN-1
0 ImagesCat. No.: HY-112477ACAS No.: 693222-51-4Synonyms: (E/Z)-Hymenialdisine analogue-1(E/Z)-Chk2-IN-1 ((E/Z)-Hymenialdisine analogue-1) (Compound 1) is a potent and selective cell cycle kinase Chk2 inhibitor with an IC50 of 8 nM. (E/Z)-Chk2-IN-1 exhibits low inhibitory activity against other kinases (such as CK1δ, MEK1, and PKCα/βⅡ) with IC50 values both >89 nM. (E/Z)-Chk2-IN-1 can be used for the research of cancer.
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MEK4 IN-4
0 ImagesCat. No.: HY-183856CAS No.: 2570386-33-1MEK4 IN-4 is a MEK4 inhibitor (IC50 = 0.041 μM) that inhibits the kinase catalytic activity of MEK4 via competitive blockade of ATP binding. MEK4 IN-4 can be used to investigate cell proliferative diseases and disorders associated with MEK4 activity, including cancer.
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Isorhamnetin (Standard)
0 ImagesIsorhamnetin (Standard) is the analytical standard of Isorhamnetin. This product is intended for research and analytical applications. Isorhamnetin is a flavonoid compound extracted from the Chinese herb Hippophae rhamnoides L.. Isorhamnetin suppresses skin cancer through direct inhibition of MEK1 and PI3K.
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GIT1-IN-1
0 ImagesCat. No.: HY-181978CAS No.: 844464-54-6GIT1-IN-1 is an inhibitor of ARF GTPase-activating protein 1 (GIT1) with a KD 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.
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NEPP11
0 ImagesCat. No.: HY-180327CAS No.: 313051-12-6NEPP11 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.
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ST-168
0 ImagesCat. No.: HY-120281CAS No.: 2126038-25-1ST-168 is an orally active MEK/PI3K inhibitor with an IC50 of 182 nM against MEK1 and IC50 values of 69.2, 41.7, 1482 and 2293 nM against PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ respectively. ST-168 completely inhibits the phosphorylation of ERK1/2 and AKT and induces cancer cell death in a 3D tumor sphere model. ST-168 demonstrates significant antitumor effects in the A375 melanoma mouse model. ST-168 improves the ocular toxicity profile of MEK inhibitors, showing lower caspase activation levels, indicating reduced apoptosis induction. ST-168 can be used in melanoma research.
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Nuvrumetinib
0 ImagesCat. No.: HY-187882CAS No.: 3079099-31-0Synonyms: PAS-004Nuvrumetinib (PAS-004) is a macrocyclic MEK inhibitor. Nuvrumetinib functionally inhibits MEK1/2, thereby suppressing pERK in tumors. Nuvrumetinib inhibits the proliferation of NRAS-mutant cancer cells. Nuvrumetinib can be used in studies related to NRASG12C-mutant solid tumors, neurofibromatosis type 1 (NF1), RASopathies and laminopathies.
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G-963
0 ImagesCat. No.: HY-182538CAS No.: 1009330-74-8G-963 is an allosteric inhibitor of mitogen-activated protein kinase kinase (MEK) with a MEK1 IC50 of 0.012 μM. G-963 interacts with Ser212 of MEK and exhibits potent antiproliferative activity against HCT116 colon cancer cells (EC50 = 0.120 μM) and A375 melanoma cells (EC50 = 0.025 μM). G-963 can be used for the research of colon cancer, melanoma.
