MNK1
MNK1 (MKNK1) encodes a MAPK-interacting serine/threonine kinase activated by ERK1 and p38 MAP kinase, placing it downstream of mitogen and stress signaling[1]. Mechanistically, eIF4G recruits MNK1 to the eIF4F complex, where MNK1 phosphorylates eIF4E at Ser209 and links MAPK activation to cap-dependent translation control[2]. In knockout systems, MNK1 and MNK2 act as exclusive eIF4E kinases, but MNK1 mainly supports inducible eIF4E phosphorylation, whereas MNK2 maintains constitutive phosphorylation[3]. This isoform distinction makes MNK1 especially relevant for stimulus-responsive translation studies rather than basal translation alone[3]. In disease models, combined Mnk1/Mnk2 deficiency delayed tumor development, and MNK inhibition blocked eIF4E phosphorylation and suppressed experimental lung metastasis outgrowth[4][5]. In hematologic experimental systems, Mnk1 regulated mRNA translation, platelet activation, megakaryocyte endomitosis, thrombopoiesis, and thrombosis[7]. For experimental applications, eFT508/tomivosertib is a potent, selective dual MNK1/2 inhibitor designed to test whether MNK blockade controls oncogenic signaling through eIF4E phosphorylation[6].
References:
- [1]. Fukunaga R, et al. MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates. EMBO J. 1997 Apr 15;16(8):1921-33. [Content Brief]
- [2]. Pyronnet S, et al. Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E. EMBO J. 1999 Jan 4;18(1):270-9. [Content Brief]
- [3]. Ueda T, et al. Mnk2 and Mnk1 are essential for constitutive and inducible phosphorylation of eukaryotic initiation factor 4E but not for cell growth or development. Mol Cell Biol. 2004 Aug;24(15):6539-49. [Content Brief]
- [4]. Ueda T, et al. Combined deficiency for MAP kinase-interacting kinase 1 and 2 (Mnk1 and Mnk2) delays tumor development. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):13984-90. [Content Brief]
- [5]. Konicek BW, et al. Therapeutic inhibition of MAP kinase interacting kinase blocks eukaryotic initiation factor 4E phosphorylation and suppresses outgrowth of experimental lung metastases. Cancer Res. 2011 Mar 1;71(5):1849-57. [Content Brief]
- [6]. Reich SH, et al. Structure-based Design of Pyridone-Aminal eFT508 Targeting Dysregulated Translation by Selective Mitogen-activated Protein Kinase Interacting Kinases 1 and 2 (MNK1/2) Inhibition. J Med Chem. 2018 Apr 26;61(8):3516-3540. [Content Brief]
- [7]. Manne BK, et al. MAPK-interacting kinase 1 regulates platelet production, activation, and thrombosis. Blood. 2022 Dec 8;140(23):2477-2489. [Content Brief]
All Product Categories
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MNK1 Related Products (23)
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Tomivosertib
0 ImagesSynonyms: eFT508Tomivosertib (eFT508) is a potent, highly selective, and orally active MNK1 and MNK2 inhibitor, with IC50s of 1-2 nM against both isoforms. Tomivosertib (eFT508) treatment leads to a dose-dependent reduction in eIF4E phosphorylation at serine 209 (IC50=2-16 nM) in tumor cell lines. Tomivosertib (eFT508) also dramatically downregulates PD-L1 protein abundance.
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Tinodasertib
0 ImagesSynonyms: ETC-206
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PROTAC MNK1 degrader-1
0 ImagesSynonyms: P11-2PROTAC MNK1 degrader-1 is a selective MNK1 PROTAC degrader with a DC50 of 11.92 nM, and a Dmax > 96% in MV4-11 cells. PROTAC MNK1 degrader-1 significantly reduces p-eIF4E (IC50: 22.07 nM), induces apoptosis, and arrests the cell cycle at the G1 phase. PROTAC MNK1 degrader-1 has potent antitumor activity. PROTAC MNK1 degrader-1 has robust antileukemic efficacy in MV4-11 xenograft mice model with acceptable drug safety.
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HD202A
0 ImagesCat. No.: HY-182046CAS No.: 2930131-74-9HD202A is an orally active, selective dual inhibitor of MNK1/MNK2 (with IC50 values of 6.09 nM and 8.06 nM, and Kd values of 1.913 μM and 5.244 μM, respectively) that inhibits the MNK-eIF4E signaling pathway. By downregulating perilipin 2 and SCD1, while upregulating adipose triglyceride lipase and PPARγ coactivator 1α, HD202A enhances mitochondrial fatty acid oxidation and redox homeostasis. HD202A effectively suppresses body weight gain, hepatic lipid accumulation and elevation of serum lipids, significantly improves glucose tolerance and insulin sensitivity of the organism, and ameliorates inflammatory features. With these comprehensive pharmacological activities, HD202A exhibits great application potential in studies of metabolic dysfunction-associated steatotic liver disease.
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MNK1/2-IN-10
0 ImagesCat. No.: HY-182939MNK1/2-IN-10 is an orally active, selective MNK1/MNK2 inhibitor, with an IC50 of 10.84 nM for MNK1 and an IC50 of 12.81 nM for MNK2. MNK1/2-IN-10 inhibits eIF4E phosphorylation, the NF-κB signaling pathway, macrophage polarization, oxidative stress and the production of pro-inflammatory cytokines. MNK1/2-IN-10 alleviates kidney and spleen damage in LPS (HY-D1056)-induced inflammatory mouse models. Anti-inflammatory agent 115 is applicable for research related to acute inflammation.
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MNK1/2-IN-11
0 ImagesCat. No.: HY-183328MNK1/2-IN-11 is a potent, selective and orally active MNK1/2 inhibitor with MNK1 IC50 of 1.2 nM, MNK2 IC50 of 1.3 nM. MNK1/2-IN-11 reduces eukaryotic translation initiation factor 4E phosphorylation, decreases Mcl-1 and Cyclin D1 expression. MNK1/2-IN-11 inhibits tumor growth in mouse CT26 colorectal tumor models. MNK1/2-IN-11 can be used for the research of colorectal cancer.
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MNK inhibitor 9
0 ImagesMNK inhibitor 9 is a potent and selective inhibitor of MNK1/2 with IC50 values of 0.003 µM and 0.003 µM for MNK1 and MNK2 respectively. MNK inhibitor 9 has good cell permeability. MNK inhibitor 9 can be used in tumor related research.
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DS12881479
0 ImagesDS12881479 is a selective non-ATP-competitive MNK1 inhibitor with an IC50 value of 387 nM. DS12881479 stabilizes MNK1 in its autoinhibited DFD-out conformation, blocks eIF4E phosphorylation, suppresses tumor cell proliferation and induces weak apoptosis. DS12881479 also inhibits FLT3 and DYRK1a kinase activity at high concentrations. DS12881479 can be used for the research of cancer, such as leukemia.
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ETP-45835
0 ImagesCat. No.: HY-W846144CAS No.: 794510-70-6ETP-45835 is slective and potent MNK inhibitor with IC50s of 575 nM and 646 nM for MNK1 and MNK2, respectively. ETP-45835 shows little activity against 24 other kinases. ETP-45835 inhibits eIF4E Ser209 phosphorylation in cells, and has anticancer effects.
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Galeterone hydrochloride
0 ImagesCat. No.: HY-70006ACAS No.: 1239339-17-3Synonyms: TOK-001 hydrochloride; VN-124-1 hydrochlorideGaleterone (TOK-001) hydrochloride is a potent, orally active molecular glue degrader, which degrades androgen receptor (AR) and its splice variants (AR-Vs) and MAP kinase-interacting serine/threonine protein kinase Mnk1/2. Galeterone hydrochloride also functions as a CYP17 inhibitor (IC50 = 47 nM). Galeterone hydrochloride induces cell apoptosis. Galeterone hydrochloride inhibits tumor growth in human prostate cancer xenograft mouse models. Galeterone hydrochloride can be used for castration resistant prostate cancer (CRPC) and pancreatic ductal adenocarcinoma (PDAC) research[1][2].
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HSN748
0 ImagesCat. No.: HY-171146CAS No.: 2409925-53-5
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HSND80
0 ImagesCat. No.: HY-172392HSND80 (Compound 1) is an orally active inhibitor of MNK/p70S6K, with Kd values of 44 nM against MNK1 and 4 nM against MNK2. HSND80 has a longer target residence time of 45 mins and 58 mins against MNK1 and MNK2 respectively. HSND80 can suppress non-small cell lung cancer (NSCLC) both in vitro and in vivo, and suppress Triple-Negative Breast Cancer (TNBC) in vitro.
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VNPP433-3β hydrochloride
0 ImagesCat. No.: HY-160777BCAS No.: 3026905-91-6Synonyms: Galeterone 3β-imidazole hydrochlorideVNPP433-3β (Galeterone 3β-imidazole) hydrochloride is an orally active molecular glue degrader, which degrades androgen receptor (AR) and its splice variants (AR-Vs) and MAP kinase-interacting serine/threonine protein kinase Mnk1/2. VNPP433-3β hydrochloride induces cell apoptosis. VNPP433-3β hydrochloride inhibits tumor growth in the CWR22Rv1 xenograft mouse model. VNPP433-3β hydrochloride can be used for the study of castration resistant prostate cancer (CRPC) and pancreatic ductal adenocarcinoma (PDAC).
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MNK1/2-IN-8
0 ImagesCat. No.: HY-158438CAS No.: 2430793-35-2
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