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- NCIT_C190059 IAO_0000115 "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." @default.
- NCIT_C190059 NCIT_A7 NCIT_C29752 @default.
- NCIT_C190059 NCIT_A7 NCIT_C68732 @default.
- NCIT_C190059 NCIT_A7 NCIT_C80031 @default.
- NCIT_C190059 NCIT_NHC0 "C190059" @default.
- NCIT_C190059 NCIT_P106 "Pharmacologic Substance" @default.
- NCIT_C190059 NCIT_P107 "IRAK4/Ikaros/Aiolos Protein Degrader KT-413" @default.
- NCIT_C190059 NCIT_P108 "IRAK4/Ikaros/Aiolos Protein Degrader KT-413" @default.
- NCIT_C190059 NCIT_P208 "CL1798834" @default.
- NCIT_C190059 NCIT_P322 "CTRP" @default.
- NCIT_C190059 NCIT_P322 "GDC" @default.
- NCIT_C190059 normalizedInformationContent "100" @default.
- NCIT_C190059 referenceCount "1" @default.
- NCIT_C190059 hasExactSynonym "IRAK4/IKZF1/IKZF3 Protein Degrader KT-413" @default.
- NCIT_C190059 hasExactSynonym "IRAK4/Ikaros/Aiolos Protein Degrader KT-413" @default.
- NCIT_C190059 hasExactSynonym "KT 413" @default.
- NCIT_C190059 hasExactSynonym "KT-413" @default.
- NCIT_C190059 hasExactSynonym "KT413" @default.
- NCIT_C190059 inSubset NCIT_C116977 @default.
- NCIT_C190059 inSubset NCIT_C116978 @default.
- NCIT_C190059 inSubset NCIT_C128784 @default.
- NCIT_C190059 inSubset NCIT_C157711 @default.
- NCIT_C190059 inSubset NCIT_C157712 @default.
- NCIT_C190059 inSubset NCIT_C176424 @default.
- NCIT_C190059 type Class @default.
- NCIT_C190059 isDefinedBy ncit.owl @default.
- NCIT_C190059 label "IRAK4/Ikaros/Aiolos Protein Degrader KT-413" @default.
- NCIT_C190059 subClassOf NCIT_C129820 @default.
- NCIT_C190059 subClassOf NCIT_C1404 @default.
- NCIT_C190059 subClassOf NCIT_C184956 @default.
- NCIT_C190059 subClassOf NCIT_C190059 @default.
- NCIT_C190059 subClassOf NCIT_C1908 @default.
- NCIT_C190059 subClassOf NCIT_C1909 @default.
- NCIT_C190059 subClassOf NCIT_C274 @default.
- NCIT_C190059 subClassOf NCIT_C308 @default.
- NCIT_C190059 subClassOf NCIT_C471 @default.
- NCIT_C190059 subClassOf NCIT_C61074 @default.