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 (24)
Related Products (24)
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MNK1/2-IN-8
0 ImagesCat. No.: HY-158438CAS No.: 2430793-35-2
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MNK1/2-IN-7
0 ImagesCat. No.: HY-163479CAS No.: 2548283-27-6MNK1/2-IN-7 (compound 20j) is an orally available inhibitor of MNK1/2 with anticancer activity and hERG safety. MNK1/2-IN-7 also inhibits the phosphorylation of eIF4E, inhibiting the MNK/eIF4E signaling pathway and cancer cell proliferation. MNK1/2-IN-7 is synergistic with Ibrutinib (HY-109970).
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NUCC-0231068
0 ImagesCat. No.: HY-184004NUCC-0231068 is a MNK1 and MNK2 inhibitor with IC50 values of 8 nM and 7 nM, respectively. NUCC-0231068 inhibits the phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) at Ser209, with an IC50 of 23 nM in its purified form and 17 nM in its D2B form. NUCC-0231068 can be used in studies related to glioblastoma.
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