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Chemical Structure| 1849590-01-7 Chemical Structure| 1849590-01-7

Structure of Tomivosertib
CAS No.: 1849590-01-7

Chemical Structure| 1849590-01-7

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eFT508 is a potent, highly selective MNK1 and MNK2 inhibitor with IC50 value of 1-2 nM.

Synonyms: eFT508

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Product Details of Tomivosertib

CAS No. :1849590-01-7
Formula : C17H20N6O2
M.W : 340.38
SMILES Code : O=C(C1=C(C)C=C(NC2=NC=NC(N)=C2)C(N13)=O)NC43CCCCC4
Synonyms :
eFT508
MDL No. :MFCD30489732
InChI Key :HKTBYUWLRDZAJK-UHFFFAOYSA-N
Pubchem ID :118598754

Safety of Tomivosertib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Tomivosertib

MAPK

Isoform Comparison

Biological Activity

Target
  • MNK2

    MNK2, IC50:1 nM

  • MNK1

    MNK1, IC50:2.4 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
MDA-MB-231 0.31 ± 0.02 nM (IC50) 24 hours Evaluate the chemosensitivity of MDA-MB-231 cells to Tomivosertib, showing that this cell line is significantly more sensitive to Tomivosertib compared to other cell lines. J Transl Med. 2022 Jun 18;20(1):276.
MDA-MB-468 1.21 ± 0.01 nM (IC50) 24 hours Evaluate the chemosensitivity of MDA-MB-468 cells to Tomivosertib, showing that this cell line is significantly more sensitive to Tomivosertib compared to other cell lines. J Transl Med. 2022 Jun 18;20(1):276.
MCF7 11.38 ± 1.02 nM (IC50) 24 hours Evaluate the chemosensitivity of MCF7 cells to Tomivosertib, showing that this cell line is significantly more sensitive to Tomivosertib compared to other cell lines. J Transl Med. 2022 Jun 18;20(1):276.
T47D 10.19 ± 0.01 nM (IC50) 24 hours Evaluate the chemosensitivity of T47D cells to Tomivosertib, showing that this cell line is significantly more sensitive to Tomivosertib compared to other cell lines. J Transl Med. 2022 Jun 18;20(1):276.
SUM149 9.14 ± 0.14 nM (IC50) 24 hours Evaluate the chemosensitivity of SUM149 cells to Tomivosertib, showing that this cell line is significantly more sensitive to Tomivosertib compared to other cell lines. J Transl Med. 2022 Jun 18;20(1):276.
Mouse dorsal root ganglion (DRG) neurons 25 nM 3 hours Tomivosertib significantly reduced spontaneous firing induced by IL-6 treatment, indicating its ability to reduce abnormal neuronal activity. Neuropsychopharmacology. 2020 Feb;45(3):524-533.
CoCaB1, CoCaB14.1, and TM01029 organoids 0.01–10 µM 72 hours To study the effect of eFT508 on high phospho-eIF4E bladder cancer organoids, results showed that high phospho-eIF4E organoids exhibited a dose-dependent decrease in cell viability in response to eFT508, while low phospho-eIF4E organoids showed no response. JCI Insight. 2021 Jun 8;6(11):e144920.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Fmr1−/− mouse model Intraperitoneal injection 1 mg/kg, 3 mg/kg, 5 mg/kg, 8 mg/kg Once daily for 4 days Tomivosertib (eFT508) reduces eIF4E phosphorylation by inhibiting MNK activity and ameliorates behavioral and physiological deficits associated with FXS in Fmr1?/? mice. Neurotherapeutics. 2021 Jan;18(1):624-639
BALB/c mice Orthotopic xenograft model IntratumOral injection 1 mg/kg/day Once daily for 8 weeks Evaluate the in vivo chemosensitivity of Tomivosertib in breast tumor xenografts, showing that both monotherapy and combination therapy with adriamycin significantly inhibited tumor growth and lung metastasis. J Transl Med. 2022 Jun 18;20(1):276.
Mice Peripheral nerve injury (PNI) model Oral (p.o.) or intraperitoneal (i.p.) 10 mg/kg Once daily for 7 days Tomivosertib reversed spontaneous pain and cognitive dysfunction in PNI mice by inhibiting the MNK-eIF4E signaling pathway, and it restored the length of axon initial segments in the prefrontal cortex. Neuropsychopharmacology. 2020 Feb;45(3):524-533.
Mice CoCaB1 and TM01029 PDX models Oral 10 mg/kg Once daily until the end of the experiment To study the effect of eFT508 on high phospho-eIF4E PDX models, results showed that high phospho-eIF4E models were sensitive to eFT508, with significantly smaller tumor size and improved survival, while low phospho-eIF4E models showed no response. JCI Insight. 2021 Jun 8;6(11):e144920.

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT03690141 Castrate-resistant Prostate Ca... More >>ncer (CRPC) Less << PHASE2 TERMINATED 2020-04-27 Yale Cancer Center, New Haven,... More >> Connecticut, 06510, United States|Northwestern University, Chicago, Illinois, 60611, United States|Kimmel Center at Johns Hopkins, Baltimore, Maryland, 21205, United States|Karmanos Cancer Institute, Detroit, Michigan, 48201, United States|Washington University, Saint Louis, Missouri, 63110, United States|Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada, 89169, United States|The Urology Group, Cincinnati, Ohio, 45212, United States|Lancaster Urology, Lancaster, Pennsylvania, 17604, United States|Carolina Urologic Research Center, Myrtle Beach, South Carolina, 29572, United States|University of Washington, Seattle, Washington, 89109, United States Less <<
NCT03318562 Triple Negative Breast Cancer|... More >>Hepatocellular Carcinoma Less << PHASE2 TERMINATED 2019-01-22 City of Hope, Duarte, Californ... More >>ia, 91010, United States|Kansas City Research Institute, Kansas City, Missouri, 64131, United States Less <<
NCT02605083 Cancer PHASE1|PHASE2 TERMINATED 2019-03-22 SCRI at HealthONE, Denver, Col... More >>orado, 80218, United States|Florida Cancer Specialists, Sarasota, Florida, 34232, United States|Tennessee Oncology, PLLC, Nashville, Tennessee, 37203, United States|MD Anderson Cancer Center, Houston, Texas, 77030, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.94mL

0.59mL

0.29mL

14.69mL

2.94mL

1.47mL

29.38mL

5.88mL

2.94mL

References

 

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