Preferred Label : Zotatifin;
NCIt synonyms : 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;
NCIt definition : 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.;
UNII : 2EWN8Z05CN;
InChIKey : QYCXWOACFWMQFO-WZWZCULESA-N;
CAS number : 2098191-53-6;
Molecule name : eFT-226; eFT 226;
NCI Metathesaurus CUI : CL978864;
Origin ID : C165746;
UMLS CUI : C5237423;
Semantic type(s)
- concept_is_in_subset
- has_target
