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^[1]. Tomivosertib (eFT508) also dramatically downregulates PD-L1 protein abundance^[2].

Tomivosertib (eFT508) reduces eIF4E phosphorylation dose-dependently at serine 209 (IC₅₀=2-16 nM) in tumor cell lines. In a panel of appr 50 hematological cancers, Tomivosertib shows anti-proliferative activity against multiple DLBCL cell lines. Sensitivity to Tomivosertib in TMD8, OCI-Ly3 and HBL1 DLBCL cell lines is associated with dose-dependent decreases in production of pro-inflammatory cytokines including TNFα, IL-6, IL-10 and CXCL10. Further evaluation Tomivosertib mechanism of action demonstrates that decreased TNFα production correlates with a 2-fold decrease in TNFα mRNA half-life^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Tomivosertib (eFT508) shows significant anti-tumor activity in the TMD8 and HBL-1 ABC-DLBCL models, both of which harbor activating MyD88 mutations. Besides, Tomivosertib combines effectively with components of R-CHOP and with novel targeted agents, including PCI-32765 and Venetoclax, in human lymphoma models^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

340.38

C₁₇H₂₀N₆O₂

1849590-01-7

Room temperature in continental US; may vary elsewhere.

DMSO : 4.35 mg/mL (12.78 mM; Need ultrasonic)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 0.44 mg/mL (1.29 mM); Clear solution

  此方案可获得 ≥ 0.44 mg/mL (1.29 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 4.4 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• 2.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 0.43 mg/mL (1.26 mM); Clear solution

  此方案可获得 ≥ 0.43 mg/mL (1.26 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 4.3 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 3.

  请依序添加每种溶剂： 5% DMSO    40% PEG300    5% Tween-80    50% saline

  Solubility: 0.4 mg/mL (1.18 mM); Suspended solution; Need ultrasonic
• 4.

  请依序添加每种溶剂： 5% DMSO    95% (20% SBE-β-CD in saline)

  Solubility: 0.4 mg/mL (1.18 mM); Suspended solution; Need ultrasonic

• [1]. Kevin R. Webster, et al. eFT508, a Potent and Selective Mitogen-Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 Inhibitor, Is Efficacious in Preclinical Models of Diffuse Large B-Cell Lymphoma (DLBCL). Blood 2015 126:1554.

  [2]. Xu Y, et al. Translation control of the immune checkpoint in cancer and its therapeutic targeting. Nat Med. 2019 Feb;25(2):301-311.