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)。

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 (IC 50 =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 (IC 90 =37 nM). Zotatifin induces cell apoptosis.

Solid

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

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.
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.
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.
Zotatifin (0.0001 μM-1 μM; 72 hours) inhibits tumor cell growth, exhibits GI50

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.
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.
has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. Peggy A. Thompson, et al. Preclinical Evaluation of eFT226, a Novel, Potent and Selective eIF4A Inhibitor with Anti-tumor Activity in B-cell Malignancies.
[2]. Gordon DE, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.Nature. 2020 Apr 30.

In Vitro: DMSO : 200 mg/mL (410.21 mM; Need ultrasonic)配制储备液