Preferred Label : IRAK4/Ikaros/Aiolos Protein Degrader KT-413;
NCIt synonyms : IRAK4/IKZF1/IKZF3 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,
IRAK4/Ikaros/Aiolos protein degrader KT-413 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.;
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
