eIF4 Inhibitor

4EGI-1 is an inhibitor of eIF4E/eIF4G interaction, with a K_d of 25 μM against eIF4E binding.

Rocaglamide (Roc-A) is isolated from the genus Aglaia and can be used for coughs, injuries, asthma and inflammatory skin diseases. Rocaglamide is a potent inhibitor of NF-κB activation in T-cells. Rocaglamide is a potent and selective heat shock factor 1 (HSF1) activation inhibitor with an IC₅₀ of ~50 nM. Rocaglamide inhibits the function of the translation initiation factor eIF4A. Rocaglamide also has anticancer properties in leukemia.

Zotatifin (eFT226) is a potent, selective, and well-tolerated eIF4A inhibitor. Zotatifin promotes eIF4A binding to specific mRNA sequences with recognition motifs in the 5’-UTRs (IC₅₀=2 nM) and interferes with the assembly of the eIF4F initiation complex. Zotatifin shows robust antiviral effects, it effectively reduces viral infectivity by inhibiting SARS-CoV-2 NP protein biogenesis (IC₉₀=37 nM). Zotatifin induces cell apoptosis.

Silvestrol is a eukaryotic translation initiation factor 4A (eIF4A) inhibitor isolated from Agave americana Linn.. Silvestrol induces autophagy and caspase-mediated apoptosis.

(S)-DMP2 is a benzoxaborole-derived photoaffinity probe that efficiently enriches eukaryotic translation initiation factor 4E (eIF4E) with stereoselectivity. (S)-DMP2 acts as a cap-binding competitive inhibitor that competes with the 7-methylguanosine cap of mRNA for binding at the cap-binding pocket of eIF4E, covalently modifies residues within this pocket, and impairs the cap-binding ability of eIF4E. (S)-DMP2 is applicable to research on eIF4E-related mechanisms and diseases.

DL149 is a component of an antibody-drug conjugate (ADC) formed by conjugating the eIF4A inhibitor FD236 (HY-186186) with an ADC linker, and exhibits potential antitumor activity. DL149 can bind to an anti-HER2 antibody to form a complete ADC molecule, which precisely binds to the HER2 receptor on the surface of tumor cells. After internalization into cells, it releases the eIF4A inhibitor payload. DL149 irreversibly blocks the mRNA translation process in tumor cells, thereby inhibiting tumor cell proliferation and inducing their death. DL149 exhibits in vivo antitumor activity in the SK-OV-3 xenograft tumor model, and can be used for the research of HER2-positive solid tumors.

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.

CR-1-31-B is a synthetic rocaglate and a potent eIF4A inhibitor. CR-1-31-B exhibits powerful inhibitory effects over eIF4A by perturbing the interaction between eIF4A and RNA, sequentially impeding initiation during protein synthesis. CR-1-31-B perturbs association of Plasmodium falciparum eIF4A (PfeIF4A) with RNA. CR-1-31-B induces apoptosis of neuroblastoma and gallbladder cancer cells.

4E1RCat is an inhibitor of cap-dependent translation, and inhibits eIF4E:eIF4GI interaction, with an IC₅₀ an of ～4 μM.

eIF4A3-IN-1 is a selective eIF4A3 inhibitor (IC₅₀: 0.26 μM; K_d: 0.043 μM) with cellular nonsense-mediated RNA decay (NMD) inhibitory activity. eIF4A3-IN-1 can specifically bind to the non-ATP binding site of eIF4A3. eIF4A3-IN-1 has anti-tumor and analgesic activities.

SBI-0640756 (SBI-756) is an inhibitor of eIF4G1 and disrupts the eIF4F complex.

eIF4A3-IN-2 is a highly selective and noncompetitive eukaryotic initiation factor 4A-3 (eIF4A3) inhibitor with an IC₅₀ of 110 nM.

Ganoderma Lucidum/Reishi Extract is a Ganoderma lucidum extract. Ganoderma Lucidum/Reishi Extract reduces the expression of c-Myc, BCL-2, BCL-XL, TERT, PDGFB, eIF4G, Survivin, β-catenin, and eIF4E. Ganoderma Lucidum/Reishi Extract downregulates the gene expression of MMP-9. Ganoderma Lucidum/Reishi Extract upregulates the expression of IL8. Ganoderma Lucidum/Reishi Extract is applicable to the research of inflammatory breast cancer. Ganoderma Lucidum is used in the research of various diseases, such as allergy, arthritis, hypertension, neurasthenia, inflammation, and cancer.

eIF4E-IN-2 is a potent inhibitor of eukaryotic initiation factor 4e (eIF4e) with an IC₅₀ of 13 nM. eIF4E-IN-2 inhibits MDA-MB-361 cells proliferation. eIF4E-IN-2 can be used for the study of breast cancer.

Briciclib (ON 014185) is a eukaryotic translation initiation factor 4E (eIF4E) inhibitor. Briciclib exhibits broad-spectrum anti-cancer activity, including in mantle cell leukemia, breast cancer, gastric cancer, and esophageal cancer cells. Briciclib reduces the expression of cyclin D1 and c-Myc, and enhances the expression of P53 and Cleaved Caspase 3 pro-apoptotic proteins. Briciclib can be used for the study of hematological system tumors and solid tumors.

4E2RCat is an inhibitor of eIF4E-eIF4G interaction with an IC₅₀ of 13.5 μM.

(Z)-4EGI-1 is the Z-isomer of 4EGI-1 and is an inhibitor of eIF4E/eIF4G interaction and of translation initiation. (Z)-4EGI-1 effectively binds to eIF4E with an IC₅₀ of 43.5 μM and a K_d value of 8.74 μM. (Z)-4EGI-1 has anticancer activity.

PROTAC MNK1 degrader-1 is a selective MNK1 PROTAC degrader with a DC₅₀ of 11.92 nM, and a D_max > 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.

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.

Episilvestrol is a derivative of silvestrol, isolated from the fruits and twigs of Aglaia perviridis, and is a specific eIF4A-targeting translation inhibitor, with antitumor activity.