Tomivosertib
Inhibitor of MKNK1, MKNK2
Structure
In Cells
(1
ratings)
In Model Organisms
(1
ratings)
note: The Chemical Probes Portal only endorses
compounds as chemical probes for use as specific and
selective modulators of the proposed target if they
receive three or more (3-4) stars.
Probe Tomivosertib is in the process of SERP review.
Please continue to check back for new reviews and commentary.
SERP ratings and comments
SERP Ratings
In Cell Rating
In Model Organisms
SERP Comments:
eFT508 / Tomivosertib is a well characterized balanced single digit nanomolar inhibitor of MKNK1 (=
MNK1) and MKNK2 (= MNK2). High selectivity was proven in a kinome selectivity screen at 1 µM
compound concentration (with CLK4 and DRAK1 as the only off-targets). Cellular and in vivo target
engagement was proven by dose-dependent inhibition of the specific downstream phosphorylation
of elF4E. In addition, dose-dependent reduction of IL-6, IL-8 and TNFalpha was observed in TMD8
cells. It is important to note that inhibition of eFT508 / Tomivosertib does not result in tumor growth
inhibition in vitro. The authors speculate that an intact in vivo tumor microenvironment is needed
for tumor growth inhibition. Indeed, eFT508 / Tomivosertib has proven in vivo efficacy in DLBCL and
solid tumor models. In line with the in vitro results inhibition of phospho-elF4E and cytokines has
been also demonstrated in vivo. PK/PD studies lead to the conclusion that at 1mg/kg dose QD (po)
produced maximal efficacy and exhibited over 80% reduction in phosho-elF4E for 8 hours. Finally, a
co-crystal structure with MNK2 is available.
(last updated: 6 Sept 2024 )