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- NCIT_C165746 IAO_0000115 "A selective inhibitor of the eukaryotic translation initiation factor 4A (eIF4A), with potential antineoplastic activity. Upon administration of zotatifin, this agent targets and binds to elF4A, and promotes eIF4A binding to mRNA with specific polypurine motifs within their 5'-untranslated region (5'-UTR), leading to the formation of a stable sequence-specific ternary complex with eIF4A and mRNA (elF4A- zotatifin-mRNA). This results in the translational repression of key oncogenes and anti-apoptotic proteins involved in tumor cell proliferation, survival and metastasis, such as KRAS, Myc, myeloid cell leukemia-1 (Mcl-1), B-cell lymphoma 2 (Bcl-2), cyclin-dependent kinase (CDK) 4 and 6, cyclin D, fibroblast growth factor receptor (FGFR) 1 and 2, human epidermal growth factor receptor 2 (HER2; ERBB2), and beta-catenin. The inhibition of the expression of these oncogenes leads to the inhibition of various oncogenic signal transduction pathways. This inhibits proliferation and induces apoptosis in tumor cells. eIF4A, a RNA helicase and the rate-limiting component of the eukaryotic translation initiation complex, catalyzes the ATP-dependent unwinding of RNA duplexes and facilitates 43S ribosome scanning within the 5'-UTR. elF4A is activated by various oncogenic signaling pathways, including RAS/mitogen-activated protein kinase (MAPK) and phosphatidylinositide 3-kinase (PI3K)/AKT pathways, and regulates the translation of oncogenes and tumor survival factors with complex secondary structures within the 5'-UTRs that are required for tumor cell proliferation, survival and metastasis." @default.
- NCIT_C165746 NCIT_A32 NCIT_C1909 @default.
- NCIT_C165746 NCIT_A7 NCIT_C178136 @default.
- NCIT_C165746 NCIT_NHC0 "C165746" @default.
- NCIT_C165746 NCIT_P106 "Pharmacologic Substance" @default.
- NCIT_C165746 NCIT_P107 "Zotatifin" @default.
- NCIT_C165746 NCIT_P108 "Zotatifin" @default.
- NCIT_C165746 NCIT_P208 "CL978864" @default.
- NCIT_C165746 NCIT_P210 "2098191-53-6" @default.
- NCIT_C165746 NCIT_P319 "2EWN8Z05CN" @default.
- NCIT_C165746 NCIT_P322 "CTRP" @default.
- NCIT_C165746 NCIT_P322 "FDA" @default.
- NCIT_C165746 NCIT_P322 "GDC" @default.
- NCIT_C165746 NCIT_P329 "800362" @default.
- NCIT_C165746 NCIT_P330 "800362" @default.
- NCIT_C165746 NCIT_P375 "Zotatifin" @default.
- NCIT_C165746 NCIT_P399 "800362" @default.
- NCIT_C165746 normalizedInformationContent "100" @default.
- NCIT_C165746 referenceCount "1" @default.
- NCIT_C165746 hasExactSynonym "4-((5aR,6S,7S,8R,8aS)-7-((Dimethylamino)methyl)-8,8a-dihydroxy-1,3-dimethoxy-6-phenyl-6,7,8,8a-tetrahydro-5aH-cyclopenta(4,5)furo(3,2-C)pyridin-5a-yl)benzonitrile" @default.
- NCIT_C165746 hasExactSynonym "ZOTATIFIN" @default.
- NCIT_C165746 hasExactSynonym "Zotatifin" @default.
- NCIT_C165746 hasExactSynonym "eFT 226" @default.
- NCIT_C165746 hasExactSynonym "eFT-226" @default.
- NCIT_C165746 inSubset NCIT_C116977 @default.
- NCIT_C165746 inSubset NCIT_C116978 @default.
- NCIT_C165746 inSubset NCIT_C128784 @default.
- NCIT_C165746 inSubset NCIT_C157711 @default.
- NCIT_C165746 inSubset NCIT_C157712 @default.
- NCIT_C165746 inSubset NCIT_C176424 @default.
- NCIT_C165746 inSubset NCIT_C177537 @default.
- NCIT_C165746 inSubset NCIT_C63923 @default.
- NCIT_C165746 type Class @default.
- NCIT_C165746 isDefinedBy ncit.owl @default.
- NCIT_C165746 label "Zotatifin" @default.
- NCIT_C165746 subClassOf NCIT_C129839 @default.
- NCIT_C165746 subClassOf NCIT_C165746 @default.
- NCIT_C165746 subClassOf NCIT_C1908 @default.
- NCIT_C165746 subClassOf NCIT_C1909 @default.
- NCIT_C165746 subClassOf NCIT_C2189 @default.
- NCIT_C165746 subClassOf NCIT_C274 @default.