1. Cell Cycle/DNA Damage
  2. Eukaryotic Initiation Factor (eIF)
  3. Zotatifin

Zotatifin (Synonyms: eFT226)

目录号: HY-112163

Zotatifin (eFT226) 是一种有效,选择性和耐受性良好的 eIF4A 抑制剂。Zotatifin 可促进 eIF4A 与 5'-UTRs 中具有识别基序的特定 mRNA 序列结合 (IC50=2 nM),并干扰 eIF4F 起始复合物的组装。Zotatifin 表现出强效的抗病毒效果,通过抑制 SARS-CoV-2 NP protein 生物合成,从而有效减少病毒传染性 (IC90=37 nM)。Zotatifin 诱导细胞凋亡 (apoptosis)。

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Zotatifin Chemical Structure

Zotatifin Chemical Structure

CAS No. : 2098191-53-6

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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[1]. Zotatifin shows robust antiviral effects, it effectively reduces viral infectivity by inhibiting SARS-CoV-2 NP protein biogenesis (IC90=37 nM)[2]. Zotatifin induces cell apoptosis[1].

IC50 & Target

IC50: 2 nM (eIF4A)[1]
IC90: 37 nM (NP-staining assay)[2]

In Vitro

Zotatifin induces the formation of a stable ternary complex [eIF4A-RNA-eFT226]. Zotatifin increases the residence time for eIF4A1 binds to an AGAGAG RNA surface, the Kd values are 0.021 μM and 8.0 μM, respectively for eFT226 presence or absence[1].
Zotatifin inhibits in vitro translation as a sequence-dependent manner, the IC50 values are 1.5 nM, 13.8 nM, 92.5 nM, and 217.5 nM, respectively in an MDA-MB-231 cell line with transiently transfected AGAGAG, GGCGGC, CCGCCG and CAACAA 5’-UTRs-containing sequences[1].
Zotatifin (0.0001 μM-1 μM; 72 hours) inhibits tumor cells growth as a dose-dependent manner. It shows a potent anti-proliferative activity (GI50<15 nM) in MDA-MB-231 tumor cells, but eIF4A1 F163L mutation rescues eFT226 anti-proliferative activity[1].
Zotatifin (0.0001 μM-1 μM; 72 hours) inhibits tumor cell growth, exhibits GI50 values for TMD8, SU-DHL-2, HBL1, Pfeiffer, SU-DHL-6, SU-DHL-10, VAL, Carnaval, U2973, Ramos, Jeko1, Mino, and Rec-1 cells are 4.1 nM, 3 nM, 5.6 nM, 3.7 nM, 5.3 nM, 7.3 nM, 6.6 nM, 4.4 nM, 4.2 nM, 4.6 nM, 7.9 nM, 11.2 nM and 11.8 nM, respectively[1].
Zotatifin (30 μM-100 μM; 3 or 24 hours) results in translational regulation of oncogenic protein, decreases MYC,CCND3,BCL2 and MCL1 protein expression as a time- and dose-dependent manner[1].
The anti-viral activity of Zotatifin is demonstrated by various assays: such as TCID50 assay, Plaque assay, NP-staining assay, et al[2].
Zotatifin (10 nM, 100 nM, 200 nM, 500 nM, 2 μM, 10 μM; 1 or 2 hours pre-treatment before virus isolates) decreases the detection of the viral NP protein and reduces viral infectivity in a concentration-dependent matter in Vero E6 cells cells infected with SARS-CoV-2 isolates[2].

Cell Viability Assay[1]

Cell Line: MDA-MB-231 tumor cells
Concentration: 0.0001 μM, 0.001 μM, 0.01 μM, 0.1 μM, 1 μM
Incubation Time: 72 hours
Result: Inhibited cell growth with a GI50 of 15 nM, and F163L mutant rescued anti-proliferative effects.

Cell Proliferation Assay[1]

Cell Line: DLBCL-ABC; DLBCL-GCB; Burkitt; and MCL tumor type cells
Concentration: 0.0001 μM, 0.001 μM, 0.01 μM, 0.1 μM, 1 μM
Incubation Time: 72 hours
Result: Inhibited cell growth with GI50 values ranging from 3 nM to 20 nM.

Cell Proliferation Assay[1]

Cell Line: TMD8 and Pfeiffer DLBCL tumor cells
Concentration: 30 μM; 100 μM
Incubation Time: 3 or 24 hours
Result: Decreased MYC, CCND3, Bcl2,and MCL1 protein levels.
In Vivo

Zotatifin (intravenous injection; 1 mg/kg; 14-22 days) decreases tumor volume, inhibits the TMD8 xenograft-bearing, HBL1 xenograft-bearing, Pfeiffer xenograft-bearing, SU-DHL-6 xenograft-bearing, SU-DHL-10 xenograft-bearing and Ramos-bearing animals’tumor growth as percentage of 97%, 87%, 70%, 83%, 37% and 75%, respectively[1].
Zotatifin (intravenous injection; 0.001 mg/kg-1 mg/kg; 15 days) inhibits the growth of B-cell lymphoma xenografts and is well-tolerated against B-cell lymphoma xenograft models in vivo[1].

Animal Model: B-cell lymphoma xenograft model[1]
Dosage: 0.001 mg/kg; 0.1 mg/kg; 1 mg/kg
Administration: Intravenous injection; 15 days
Result: Showed efficacy in B-cell lymphoma xenograft models.
Molecular Weight









Room temperature in continental US; may vary elsewhere.


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ZotatifineFT226eFT 226eFT-226Eukaryotic Initiation Factor (eIF)SARS-CoVApoptosisSARS coronavirusInhibitorinhibitorinhibit


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