MNK2
MNK2 is a MAPK-interacting serine/threonine kinase that phosphorylates eIF4E at Ser209 and supports basal, constitutive eIF4E phosphorylation, whereas MNK1 mainly mediates inducible phosphorylation after MAPK activation[1]. Mechanistically, MNK2 connects ERK/p38 signaling to translation control, making MNK2-eIF4E a practical axis for studying stress- and growth-linked protein synthesis[1][2]. In disease models, MNK2 overexpression in NSCLC was associated with proliferation, migration, invasion, lymph node metastasis, and lower overall survival through phosphorylated eIF4E signaling[3]. Compared with related isoforms, Mnk2a contains a MAPK-binding domain, activates p38α-MAPK, and suppresses Ras-induced transformation, whereas Mnk2b lacks this activity and enhances eIF4E phosphorylation[2]. Human MNK2 splice-variant termini also determine kinase activity and subcellular localization, supporting isoform-specific experimental design[4]. For inhibitor studies, eFT508/tomivosertib is a selective MNK1/2 inhibitor that reduces eIF4E Ser209 phosphorylation and enables pharmacodynamic assessment of MNK blockade[5].
References:
- [1]. 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]
- [2]. Maimon A, et al. Mnk2 alternative splicing modulates the p38-MAPK pathway and impacts Ras-induced transformation. Cell Rep. 2014 Apr 24;7(2):501-513. [Content Brief]
- [3]. Guo Z, et al. MAP kinase-interacting serine/threonine kinase 2 promotes proliferation, metastasis, and predicts poor prognosis in non-small cell lung cancer. Sci Rep. 2017 Sep 6;7(1):10612. [Content Brief]
- [4]. Scheper GC, et al. The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization. Mol Cell Biol. 2003 Aug;23(16):5692-705. [Content Brief]
- [5]. 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]
All Product Categories
-
MNK2 Related Products (20)
Related Products (20)
- 1
-
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.
-
Tinodasertib
0 ImagesSynonyms: ETC-206
-
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.
-
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.
-
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.
-
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.
-
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.
-
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].
-
HSN748
0 ImagesCat. No.: HY-171146CAS No.: 2409925-53-5
-
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.
-
K783-0308
0 ImagesCat. No.: HY-115906CAS No.: 422554-29-8K783-0308 is a potent and selective dual inhibitor of FLT3 and MNK2 with IC50 values of 680 and 406 nM, respectively. K783-0308 inhibits the growth of MOLM-13 (IC50=10.5 µM) and MV-4-11 (IC50=10.4 µM) cells. K783-0308 promotes acute myeloid leukemia (AML) cell apoptosis and cell cycle arrests in the G0/G1 phase.
-
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).
-
MNK1/2-IN-8
0 ImagesCat. No.: HY-158438CAS No.: 2430793-35-2
-
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).
-
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.
- 1
