Preferred Label : Irinotecan/P-glycoprotein Inhibitor HM30181AK Combination Tablet;
NCIt definition : An orally bioavailable combination tablet containing the semisynthetic camptothecin
derivative irinotecan and the multidrug resistance (MDR) efflux pump P-glycoprotein
(P-gp) inhibitor HM30181AK, with potential antineoplastic activity. HM30181A binds
to P-gp and prevents the P-gp-mediated efflux of irinotecan from tumor cells, which
may result in greater intracellular concentrations of irinotecan and enhanced cytotoxicity.
Retained intracellularly, the prodrug irinotecan is converted, by a carboxylesterase-converting
enzyme, to the biologically active metabolite 7-ethyl-10-hydroxy-camptothecin (SN-38).
SN-38 inhibits topoisomerase I activity by stabilizing the cleavable complex between
topoisomerase I and DNA, resulting in DNA breaks that inhibit DNA replication and
trigger apoptotic cell death. P-gp, encoded by the MDR-1 gene, is a member of the
ATP-binding cassette (ABC) superfamily of transmembrane transporters and is overexpressed
by some MDR tumors, preventing the intracellular accumulation of various cytotoxic
agents.;
Drug name : Oratecan;
NCI Metathesaurus CUI : CL412470;
Origin ID : C88280;
UMLS CUI : C2981802;
Semantic type(s)
- concept_is_in_subset
