Preferred Label : Beta-lapachone Prodrug ARQ 761;
NCIt definition : A synthetic, soluble prodrug of beta-lapachone, a poorly soluble, ortho-naphthoquinone
with potential antineoplastic and radiosensitizing activity. ARQ 761 is converted
to beta-lapachone (b-lap) in vivo. When b-lap is activated by NAD(P)H:quinone oxidoreductase-1
(NQO1) this agent creates a futile oxidoreduction, generating highly reactive oxygen
species (ROS) that results in DNA damage. The activation of b-lap also causes hyperactivation
of poly (ADP-ribose) polymerase-1 (PARP-1), an enzyme that facilitates DNA repair,
accompanied by rapid depletion of NAD /ATP nucleotide levels. As a result, a caspase-independent
and endoplasmic reticulum (ER) stress-induced mu-calpain-mediated cell death occurs
in NQO1-overexpressing tumor cells. In addition, b-lap induces expression of the checkpoints
activator E2F transcription factor 1 (E2F1) and thereby activates the E2F1-mediated
checkpoint pathway that directly triggers apoptosis. As ARQ 761 is soluble and requires
less solvent, this formulation may cause less hemolytic anemia associated with administration
of the synthetic b-lap ARQ 501.;
Molecule name : ARQ 761;
NCI Metathesaurus CUI : CL432960;
Origin ID : C99146;
UMLS CUI : C3274562;
Semantic type(s)
- concept_is_in_subset
