| Size | Price | Stock | Qty |
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| 100μg |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Zotatifin targets eukaryotic translation initiation factor 4A (eIF4A), an RNA helicase that unwinds secondary structures in the 5' untranslated regions (UTRs) of mRNAs to facilitate ribosome recruitment and translation initiation. By inhibiting eIF4A, Zotatifin selectively suppresses the translation of mRNAs with complex 5'-UTR structures, including many oncogenes.
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| ln Vitro |
Zotatifin causes the stable ternary complex [eIF4A-RNA-eFT226] to form. In the presence or absence of eFT226, ozotifin lengthens the residence duration of eIF4A1 bound to the AGAGAG RNA surface, with Kd values of 0.021 μM and 8.0 μM [1]. has sequence-dependent inhibition of in vitro translation, with IC50 values in the MDA-MB-231 cell line of 1.5 nM, 13.8 nM, 92.5 nM, and 217.5 nM. temporarily transfected with 5'-UTRs for AGAGAG, GGCGGC, CCGCCG, and CAACAA. In a dose-dependent manner, zotatifin (0.0001 μM-1 μM; 72 hours) suppresses the development of tumor cells. It exhibits strong anti-apoptotic action in MDA-MB-231 tumor cells (GI50<15 nM). Zotatifin (0.0001 μM-1 μM; 72 hours) suppresses the proliferation of tumor cells against TMD8, SU-DHL-2, HBL1, Pfeiffer, and SU-DHL-; however, the anti-proliferative action of eFT226 is abruptly relieved by eIF4A1 F163L [1]. GI50 value 6, SU-DHL-10, VAL, Carnaval, U2973, Ramos, Jeko1, Mino, and Rec-1 cells have the following performance values: 4.1 nM, 3 nM, 5.6 nM, 3.7 nM, 5.3 nM, 7.3 nM, and 6.6 nM, in that order. The transformation regulatory protein of coconut genes is induced by zotatifin (30 μM-100 μM; 3 or 24 hours) in a dose- and time-dependent manner. Zotatifin's antiviral efficacy is evaluated using a number of certified tests, including the TCID50 assay, plaque assay, NP-staining assay, and others [2]. Less viral NP protein and less concentration were found in Vero E6 cells infected with SARS-CoV-2 isolates at concentrations of 100 nM, 200 nM, 500 nM, 2 μM, and 10 μM; 1 or 2 hours prior to virus isolation.
In vitro, Zotatifin is a highly effective and sequence-selective inhibitor of eIF4A, with an IC50 of 2 nM. It promotes eIF4A binding to specific mRNA sequences and disrupts the assembly of the eIF4F initiation complex. The compound induces cell apoptosis and inhibits Sox4 translation. |
| ln Vivo |
In TMD8 xenografts, HBL1-bearing xenografts, Pfeiffer-bearing xenografts, and SU-DHL-6-bearing xenografts, zogafitin (IV; 1 mg/kg; 14–22 days) decreases tumor size and inhibits plaques. The percentages of tumor growth in SU-DHL-10 xenograft- and Ramos-bearing animals were 97%, 87%, 70%, 83%, 37%, and 75%, respectively [1]. In B-cell-localized xenograft models, zogafitin (IV; 0.001 mg/kg-1 mg/kg; 15 days) is well tolerated and reduces the growth of B-cell-localized xenografts [1].
In vivo, Zotatifin has antitumor activity, blocking tumor growth driven by receptor tyrosine kinases. It has been reported to inhibit translation of driver oncogenes in models of lymphoma and exhibits antiviral activity by impacting viral protein translation and replication. |
| Enzyme Assay |
In vitro enzyme inhibition assays for Zotatifin are performed using purified eIF4A protein. The helicase activity of eIF4A is measured in the presence of increasing concentrations of the compound, using RNA substrates and ATP. The inhibition of RNA unwinding is quantified, and the IC50 (2 nM) is calculated from the inhibition curve.
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| Cell Assay |
Cell viability assay [1]
Cell Types: MDA-MB-231 tumor cell Tested Concentrations: 0.0001μM, 0.001μM, 0.01μM, 0.1μM, 1μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibition of viral infectivity of cells [2]. The F163L mutant rescued the antiproliferative effect of growth with a GI50 of 15 nM. Cell proliferation assay[1] Cell Types: DLBCL-ABC; DLBCL-GCB; Burkitt; and MCL Tumor Type Cell Tested Concentrations: 0.0001 μM, 0.001 μM, 0.01 μM, 0.1 μM, 1 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibition Cell growth, GI50 values range from 3 nM to 20 nM. Cell proliferation experiment [1] Cell Types: TMD8 and Pfeiffer DLBCL Tumor cell Tested Concentrations: 30 μM; 100 μM Incubation Duration: 3 or 24 hrs (hours) Experimental Results: MYC, CCND3, Bcl2 and MCL1 protein levels were diminished. In vitro cellular assays for Zotatifin are performed using cancer cell lines, such as lymphoma or other models. Cells are treated with the compound, and translation of specific mRNAs (e.g., oncogenes with complex 5'-UTRs) is measured using reporter assays or Western blotting. Cell viability, apoptosis, and proliferation are assessed using standard assays. |
| Animal Protocol |
Animal/Disease Models: B-cell lymphoma xenograft model [1]
Doses: 0.001 mg/kg; 0.1 mg/kg; 1 mg/kg Route of Administration: intravenous (iv) (iv)injection; 15-day Experimental Results: In B-cell lymphoma xenograft model Show efficacy. In vivo animal experiments for Zotatifin are conducted in mouse xenograft models of tumors driven by receptor tyrosine kinases. A typical protocol involves administration of the compound via intraperitoneal or oral routes, followed by measurement of tumor volume, assessment of target engagement (e.g., eIF4A inhibition), and analysis of apoptosis markers. |
| ADME/Pharmacokinetics |
The pharmacokinetic properties of Zotatifin have been characterized in preclinical studies. The compound has a molecular weight of 487.55, molecular formula C28H29N3O5, and is soluble in DMSO (≥100 mg/mL). It should be stored at 2-8°C. Further PK details, including half-life, bioavailability, and tissue distribution, are available from the manufacturer's data sheets.
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| Toxicity/Toxicokinetics |
Toxicological data for Zotatifin are not extensively reported in the available literature. As a research-use compound, its safety profile has not been formally evaluated in comprehensive preclinical toxicology studies. The compound is intended for research purposes only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
Zotatifin is being investigated in the clinical trial NCT04092673 (Eft226 in patients with specific advanced solid tumors). Zotatifin is a selective inhibitor of eukaryotic translation initiation factor 4A (eIF4A) with potential antitumor activity. After administration, Zotatifin targets and binds to eIF4A, promoting the binding of eIF4A to mRNAs containing specific polypurine motifs within the 5' untranslated region (5'-UTR), thereby forming a stable sequence-specific ternary complex (eIF4A-zotatifin-mRNA). This leads to the inhibition of translation of key oncogenes and anti-apoptotic proteins involved in tumor cell proliferation, survival, and metastasis, such as KRAS, Myc, myeloid leukemia-1 (Mcl-1), B-cell lymphoma-2 (Bcl-2), cyclin-dependent kinases (CDKs) 4 and 6, cyclin D, fibroblast growth factor receptor (FGFR) 1 and 2, human epidermal growth factor receptor 2 (HER2; ERBB2), and β-catenin. The inhibition of these oncogene expression results in the suppression of multiple oncogenic signaling pathways, thereby inhibiting tumor cell proliferation and inducing apoptosis. eIF4A is an RNA helicase and a rate-limiting component of the eukaryotic translation initiation complex. It catalyzes ATP-dependent RNA double-strand unwinding and promotes the scanning of 43S ribosomes within the 5' untranslated region (5'-UTR). eIF4A can be activated by multiple oncogenic signaling pathways, including the RAS/mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, and regulates the translation of oncogenes and tumor survival factors with complex secondary structures in the 5'-UTR. These genes and factors are essential for the proliferation, survival and metastasis of tumor cells.
Zotatifin is also known as eFT226. It is a selective eIF4A inhibitor with antiviral and anticancer activities. It promotes eIF4A binding to specific mRNA sequences and interferes with the assembly of the eIF4F initiation complex. This product is for research use only. |
| Molecular Formula |
C28H29N3O5
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| Molecular Weight |
487.5470
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| Exact Mass |
487.21
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| CAS # |
2098191-53-6
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| Related CAS # |
rel-Zotatifin;2098191-54-7
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| PubChem CID |
129138801
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| Appearance |
White to off-white solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
36
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| Complexity |
819
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| Defined Atom Stereocenter Count |
5
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| SMILES |
O1C2=C([H])C(=NC(=C2[C@@]2([C@@]([H])([C@]([H])(C([H])([H])N(C([H])([H])[H])C([H])([H])[H])[C@@]([H])(C3C([H])=C([H])C([H])=C([H])C=3[H])[C@]12C1C([H])=C([H])C(C#N)=C([H])C=1[H])O[H])O[H])OC([H])([H])[H])OC([H])([H])[H]
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| InChi Key |
QYCXWOACFWMQFO-WZWZCULESA-N
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| InChi Code |
InChI=1S/C28H29N3O5/c1-31(2)16-20-23(18-8-6-5-7-9-18)28(19-12-10-17(15-29)11-13-19)27(33,25(20)32)24-21(36-28)14-22(34-3)30-26(24)35-4/h5-14,20,23,25,32-33H,16H2,1-4H3/t20-,23-,25-,27+,28+/m1/s1
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| Chemical Name |
4-[(2S,3R,4S,5S,6R)-4-[(dimethylamino)methyl]-2,3-dihydroxy-10,12-dimethoxy-5-phenyl-7-oxa-11-azatricyclo[6.4.0.02,6]dodeca-1(12),8,10-trien-6-yl]benzonitrile
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~200 mg/mL (~410.21 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (10.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (10.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0511 mL | 10.2554 mL | 20.5107 mL | |
| 5 mM | 0.4102 mL | 2.0511 mL | 4.1021 mL | |
| 10 mM | 0.2051 mL | 1.0255 mL | 2.0511 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Link: https://clinicaltrials.gov/ct2/show/NCT05101564
Conditions:Breast Cancer|HER2-negative Breast Cancer|ER Positive Breast CancerLink: https://clinicaltrials.gov/ct2/show/NCT03675893
Conditions:Endometrial Cancer|Ovarian CancerLink: https://clinicaltrials.gov/ct2/show/NCT04092673
Conditions:Solid Tumor, Adult
Title:Intravenous Zotatifin in Adults With Mild or Moderate COVID-19
Status:Completed
updateDate:2023-10-05
Ctid:NCT04632381
Link: https://clinicaltrials.gov/ct2/show/NCT04632381
Conditions:Corona Virus InfectionProducts are for research use only; We do not sell to patients
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