Preferred Label : Zomiradomide;
NCIt synonyms : IRAK4/IKZF1/IKZF3 Protein Degrader KT-413; IRAK4/Ikaros/Aiolos Protein Degrader KT-413;
NCIt definition : A small molecule protein degrader of interleukin-1 receptor-associated kinase 4 (IRAK4)
and the immunomodulatory imide drug (IMiD) substrates Ikaros (IKZF1) and Aiolos (IKZF3),
with potential immunomodulating and antineoplastic activities. Upon administration,
zomiradomide modulates the E3 (ubiquitin) ligase and targets IRAK4, Ikaros and Aiolos
for ubiquitination. This induces proteasome-mediated degradation of IRAK4, Ikaros
and Aiolos. The degradation of IRAK4 inhibits IRAK4-mediated signaling and prevents
the activation of IRAK4-mediated nuclear factor-kappa B (NF-kB) signaling and decreases
the expression of inflammatory cytokines and certain pro-survival factors. This inhibits
the proliferation of IRAK4-overactivated tumor cells, which are found in cells harboring
MYD88 activating mutations or those with overactivated toll-like receptor (TLR) pathways.
The degradation of the transcription factors Ikaros and Aiolos leads to a downregulation
of other proteins, including interferon regulatory factor 4 (IRF4), which upregulates
type I interferon signaling and further inhibits NF-kB activation. This leads to apoptosis
and the inhibition of tumor cell proliferation. IRAK4, a serine/threonine-protein
kinase that plays a key role in both the TLR and IL-1R signaling pathways, is activated
though the adaptor protein MYD88 and links the TLR and IL-1R signaling pathway to
the NF-kB pathway.;
UNII : AQ5UXV5646;
CAS number : 2655656-99-6;
Molecule name : KT 413; KT-413;
NCI Metathesaurus CUI : CL1798834;
Origin ID : C190059;
UMLS CUI : C5783474;
Semantic type(s)
- concept_is_in_subset
- has_target
