MNK1 Inhibitor

Tomivosertib (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.

CGP 57380 is a cell-permeable pyrazolo-pyrimidine compound that acts as a selective inhibitor of Mnk1 with IC₅₀ of 2.2 μM, but has no inhibitory activity against p38, JNK1, ERK1/2, PKC, or Src-like kinases.

Tinodasertib (ETC-206) is a selective MNK1 and MNK2 inhibitor with IC₅₀s of 64 nM and 86 nM, respectively.

SLV-2436 is a highly potent and ATP-competitive inhibitor of MNK1 and MNK2 with IC₅₀s of 10.8 nM and 5.4 nM, respectively.

HD202A is an orally active, selective dual inhibitor of MNK1/MNK2 (with IC₅₀ values of 6.09 nM and 8.06 nM, and K_d 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 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 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.

EB1 is the inhibitor of kinases MNK with IC₅₀s of 0.69 μM (MNK1) and 9.4 μM (MNK2). EB1 selectively inhibits the growth of cancer cells, but not normal cells. EB1 also increases cell apoptosis and suppresses eIF4E phosphorylation.

MNK 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.

DS12881479 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.

ETP-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.

MNK1 ligand 1 (Compound 5) is a MNK1 ligand. MNK1 ligand 1 can be used for synthesis of PROTAC MNK1 degrader-1 (HY-176428).

ETC-168 is a selective and oral active MNK inhibitor with the IC₅₀ values of 23 and 43 nM against MNK1 and MNK2, respectively. ETC-168 shows antiproliferative efficacy in vivo and in vitro.

HSN748 is a Ponatinib (HY-12047) analogue and a multikinase inhibitor. HSN748 has inhibitory activity on FLT3, ABL1, RET, PDGFRα/β, MNK1, MNK2 and other kinases. HSN748 can inhibit the growth of chronic myeloid leukemia and acute myeloid leukemia cell lines and can be used in the study of leukemia.

HSND80 (Compound 1) is an orally active inhibitor of MNK/p70S6K, with K_d 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.

MNK1/2-IN-6 is a potent and selective MNK1/2 inhibitor with IC₅₀s of 2.3 nM and 3.4 nM for MNK1 and MNK2, respectively. MNK1/2-IN-6 induces apoptosis in a concentration-dependent manner.

YTB53 is a MNK1 and MNK2 inhibitor with IC₅₀s of 37 nM and 9 nM, respectively. YTB53 inhibits PDGFRα, TRKB and FLT3 in leukemia cells. YTB53 induces cell cycle arrest, apoptosis, pyroptosis, and mitochondrial dysfunction. YTB53 exhibits antiangiogenic effects. YTB53 can be used for the study of acute myeloid leukemia (AML).

MNK1/2-IN-8 (compound 15b) is a MNK1/2 inhibitor with the IC₅₀ values of 0.8 and 1.5 nM against Mnk1 and Mnk2. MNK1/2-IN-8 shows anti-proliferative activity and induces cell cycle arrest.

MNK1/2-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 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.