Preferred Label : AKR1C3-activated Prodrug AST-3424;
NCIt synonyms : Aldo-keto Reductase 1c3-activated Prodrug OBI-3424; AKR1C3-activated Prodrug TH-3424; AKR1C3-activated Prodrug OBI-3424;
NCIt related terms : AST-3424;
NCIt definition : A small-molecule nitro-benzene, aldo-keto reductase 1C3 (AKR1C3)-activated prodrug
of N,N'-bisethylenephosphoramidate, a DNA bis-alkylating agent, with potential antineoplastic
activity. Upon intravenous administration, AKR1C3-activated prodrug AST-3424 is converted
to its active form by AKR1C3, which is upregulated in certain tumor cell types while
not expressed in normal healthy cells. The active metabolite selectively binds to
and alkylates DNA in AKR1C3-overexpressing tumor cells, resulting in DNA base pair
mismatching, interstrand crosslinking and inhibition of DNA repair and synthesis,
cell-cycle arrest, and apoptosis. As the expression of AKR1C3 is restricted to tumors,
AST-3424 is selectively converted to its active metabolite in tumor cells only while
its conversion in normal, healthy tissue is absent; this allows for an increased cytotoxic
effect of the alkylating agent in tumor cells while decreasing its toxicity.;
UNII : X6SH5T8H76;
CAS number : 2097713-68-1;
Molecule name : TH 3424; TH-3424; OBI 3424; OBI-3424;
NCI Metathesaurus CUI : CL563114;
Origin ID : C156414;
UMLS CUI : C4744805;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- chemical_or_drug_has_physiologic_effect
- concept_is_in_subset
- has_target
