MNK 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.

HG-10-102-01 is a highly potent, selective, and brain-penetrable LRRK2 inhibitor, with IC₅₀ values of 20.3 and 3.2 nM against wild-type LRRK2 and LRRK2[G2019S], respectively. HG-10-102-01 also inhibits MNK2 and MLK1, with IC₅₀ values of 0.6 and 2.1 μM. HG-10-102-01 can be used for Parkinson's disease (PD) research.

ETC-501 is a blood-brain barrier-permeable, orally active, and selective MNK1/MNK2 inhibitor, with an IC₅₀ of 0.033 μM against MNK1 and 0.111 μM against MNK2. ETC-501 inhibits glioblastoma cell proliferation, impairs DNA damage repair function, delays cell cycle progression, and suppresses ribosome biogenesis. ETC-501 enhances Temozolomide (HY-17364)-induced cellular senescence, attenuates the senescence-associated secretory phenotype, and increases cellular sensitivity to Navitoclax (HY-10087). ETC-501 is applicable to research related to glioblastoma.

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.

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.

QL-X-138 is a potent and selective BTK/MNK dual kinase inhibitor, exhibits covalent binding to BTK and non-covalent binding to MNK. QL-X-138 shows IC₅₀s of 9.4 nM, 107.4 nM and 26 nM for BTK, MNK1 and MNK2 kinases respectively. QL-X-138 also shows anti-dengue virus 2 activity, with an IC₅₀ of 3.5 μM. QL-X-138 can be used for the research of B-cell malignancies.

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.

Cercosporamide is a highly potent, ATP-competitive PKC kinase inhibitor targeting to PKC1, with an IC₅₀ of <50 nM and a K_i of <7 nM. Cercosporamide is a unique Mnk inhibitor.

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.

MNK-IN-5 is a MNK inhibitor that suppresses MNK activity.

MNK1/2-IN-5 is a potent and selective MNK1/2 inhibitor as a therapeutic agent.

Tomivosertib hydrochlorideis a potent, highly selective, and orally active MNK1 and MNK2 inhibitor, with IC₅₀s of 1-2 nM against both isoforms. Tomivosertib hydrochloride treatment leads to a dose-dependent reduction in eIF4E phosphorylation at serine 209 (IC₅₀=2-16 nM) in tumor cell lines. Tomivosertib hydrochloride also dramatically downregulates PD-L1 protein abundance.

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.

MNK-IN-4 (compound D25) is a potent and selective MNK inhibitor for the study of sepsis-related acute splenic injury.

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.