Preferred Label : SIK3 Inhibitor OMX-0407;
NCIt synonyms : Salt-inducible Kinase 3 Inhibitor OMX-0407;
NCIt definition : An orally bioavailable inhibitor of the salt-inducible kinase 3 (SIK3), with potential
antineoplastic and chemosensitizing activities. Upon oral administration, SIK3 inhibitor
OMX-0407 targets, binds to and blocks the activity of SIK3. This prevents SIK3-mediated
signaling, inhibits SIK3-triggered phosphorylation of histone deacetylase 4 (HDAC4)
and inhibits the associated transcriptional activity of NF-kB. This inhibits pro-survival
signaling mediated by SIK3-HDAC4-nuclear factor kappa B (NF-kB) signaling and potentiates
death receptor (DR)-mediated apoptosis in SIK3-overexpressing tumor cells. OMX-0407
may enhance tumor sensitivity to other chemotherapeutic agents. In addition, OMX-0407
repolarizes the tumor microenvironment (TME) by strongly decreasing regulatory T-cells
(Tregs) and M2-polarized macrophages while not affecting the peripheral T-cells. This
reduces the immunosuppressive TME and increases cytotoxic T-cell activity, thereby
inducing an anti-tumor immune response. SIK3, a serine/threonine kinase belonging
to the AMP-activated protein kinase (AMPK)-related family, is required for bipolar
mitotic spindle formation; it is overexpressed in a variety of tumor cell types. It
also promotes NF-kB nuclear translocation and stabilization and activation, leading
to increased tumor cell survival.;
Molecule name : OMX-0407; OMX 0407;
NCI Metathesaurus CUI : CL1907475;
Origin ID : C200466;
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