Preferred Label : Locnartecan;
NCIt synonyms : HDC SN-38; HSP90-targeted SN-38 Conjugate PEN-866;
NCIt definition : A miniature drug conjugate composed of the irinotecan metabolite 7-ethyl-10-hydroxy-camptothecin
(SN-38) conjugated, through a cleavable linker, to a ligand of chaperone protein heat
shock protein 90 (Hsp90), with potential antineoplastic activity. Upon administration
of locnartecan, the HSP90 ligand moiety targets HSP90, which allows the conjugate
to penetrate, accumulate and be retained in the tumor cell. Once the linker is cleaved,
the SN-38 moiety is released in a sustained manner. SN-38 then binds to and inhibits
topoisomerase I by stabilizing the cleavable complex between topoisomerase I and DNA,
which results in DNA breaks, inhibition of DNA replication and apoptosis. Compared
to SN-38 alone, locnartecan preferentially targets, accumulates and is retained in
the tumor cells due to its binding to Hsp90, which results in increased concentrations
of SN-38 at the tumor site. This allows sustained release of SN-38 and leads to increased
and prolonged efficacy while reducing toxicity to normal, healthy tissues. Hsp90,
a chaperone protein upregulated and activated in a variety of tumor cells compared
to normal healthy tissue, regulates the folding, stability and degradation of many
oncogenic signaling proteins.;
UNII : 56DL1J49LR;
CAS number : 1472614-83-7; a href https://gsrs.ncats.nih.gov/ginas/app/beta/browse-substance?search 1472614-83-7
alt lien vers site G-SRS target _blank img src /img/logos/logo_g-srs.png alt Logo
G-SRS /a ;
Molecule name : STA-8666; PEN-866; STA-12-8666; PEN 866;
NCI Metathesaurus CUI : CL601355;
Origin ID : C151953;
UMLS CUI : C5667169;
Semantic type(s)
- concept_is_in_subset
- has_target
