Tomivosertib (eFT-508)

Name: Tomivosertib (eFT-508)
Brand: Selleck Chemicals
SKU: S8275
Rating: 5 (2 reviews)

For research use only.

Catalog No.S8275

2 publications

Tomivosertib (eFT-508) Chemical Structure

CAS No. 1849590-01-7

Tomivosertib (eFT-508) is a potent and selective MNK1/2 inhibitor with IC50s of 2.4 nM and 1 nM, respectively. It potentially results in decreased tumor cell proliferation and tumor growth. Tomivosertib (eFT-508) inhibits eIF4E phosphorylation and dramatically downregulates PD-L1 protein abundance.

Selleck's Tomivosertib (eFT-508) has been cited by 2 publications

Purity & Quality Control

Choose Selective MNK Inhibitors

Biological Activity

Description

Tomivosertib (eFT-508) is a potent and selective MNK1/2 inhibitor with IC50s of 2.4 nM and 1 nM, respectively. It potentially results in decreased tumor cell proliferation and tumor growth. Tomivosertib (eFT-508) inhibits eIF4E phosphorylation and dramatically downregulates PD-L1 protein abundance.

Targets

MNK2 ^[1] (Cell-free assay)	MNK1 ^[1] (Cell-free assay)
1 nM	2.4 nM

In vitro

eFT508 has a half-maximal inhibitory concentration (IC50) of 1-2 nM against both MNK isoforms in enzyme assays and inhibits the kinase through a reversible, ATP-competitive mechanism of action. Treatment of tumor cell lines with eFT508 leads to a dose-dependent reduction in eIF4E phosphorylation at serine 209 (IC50 = 2-16 nM). In a panel of ~50 hematological cancers, eFT508 shows anti-proliferative activity against multiple DLBCL cell lines. Sensitivity to eFT508 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^[1].

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
TMD8	NVfVUm5xTnWwY4Tpc44h[XO\|YYm=	MoqyNE4xOSxiMD6xMEAyNCB\|IHHu[EAyOCEQvF2=	NILpdJkzKGh?	NUSwOog5eG:2ZX70JIRwe2VvZHXw[Y5l\W62IHnubIljcXSrb36gc4Yh\UmINFWgV4VzOjB7IIDoc5NxcG:{eXzheIlwdg>?	NI\MUnMzQTV{NkC5PC=>
TMD8	M36yW3Bzd2yrZnXyZZRqd25iYYPzZZk>		NVTCVG9yOTJiaB?=	NEHKPGRKSzVyPUKuOVMh\|ryP	NXXUcY5DOzB6MkSxOlc>
MV4-11	NEnT[lBRem:uaX\ldoF1cW:wIHHzd4F6		NUPZdYJVOTJiaB?=	M1rP[WlEPTB;MUSuOFkh\|ryP	MX2zNFgzPDF4Nx?=
K562	M1nJVHBzd2yrZnXyZZRqd25iYYPzZZk>		NETCTmgyOiCq	NFraXoFKSzVyPUGzMlU1KM7:TR?=	NXS3[4FEOzB6MkSxOlc>

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	p-eIF4E; PubMed: 30459229 J Neurosci eFT508 significantly reduced the level of eIF4E phosphorylation at 0.1 and 1 μM after 1 hr, without affecting other signaling pathways in cultured mouse DRG neurons.	30459229
Growth inhibition assay	Cell viability; PubMed: 30832411 Cancers (Basel) Head-to-head antiproliferative effects of VNLG-152R and eFT508 on MDA-MB-231 and MDA-MB-468 cells. The dose-response curves were generated from MTT assays after 6-day exposure to different concentrations of the compounds. Each point is a mean of replicates from three independent experiments.	30832411

In vivo

eFT508 is well-tolerated and shows efficacy against MyD88-mutant DLBCL models in vivo. Significant anti-tumor activity of eFT508 is observed in the TMD8 and HBL-1 ABC-DLBCL models(subcutaneous human lymphoma xenograft models), both of which harbor activating MyD88 mutations^[1].

Protocol

Cell Research: ^[1]	- Collapse Cell lines: TMD8 cells Concentrations: 0.01, 0.1, 1, 3, 10 μM Incubation Time: 24 h Method: TMD8 cells are treated with the indicated concentrations of eFT508 for 24 h. Cell lysates are subjected to m7-GTP Sepharose pull-down and bound proteins are analyzed by immunoblotting with the indicated antibodies. (Only for Reference)

References

[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). Abstract#1554.

Solubility (25°C)

In vitro	DMSO	13 mg/mL (38.19 mM)
	Water	Insoluble
	Ethanol	Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download Tomivosertib (eFT-508) SDF

Molecular Weight	340.38
Formula	C₁₇H₂₀N₆O₂
CAS No.	1849590-01-7
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CC1=C2C(=O)NC3(N2C(=O)C(=C1)NC4=NC=NC(=C4)N)CCCCC3

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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2020-09-01)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04261218	Recruiting	Drug: tomivosertib\|Drug: paclitaxel	Breast Cancer	Translational Research in Oncology\|Effector Therapeutics\|Stand Up To Cancer	August 2020	Phase 1
NCT02937675	Terminated	Drug: Tomivosertib (eFT-508)	Lymphoma	Effector Therapeutics	February 8 2017	Phase 1\|Phase 2
NCT02605083	Terminated	Drug: eFT508	Cancer	Effector Therapeutics	December 3 2015	Phase 1\|Phase 2

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Tomivosertib (eFT-508)