Preferred Label : Fosciclopirox;
NCIt synonyms : Ciclopirox Prodrug CPX-POM; Ciclopirox-POM; Ciclopirox Prodrug;
NCIt definition : A phosphoryloxymethyl (POM) ester-based prodrug of ciclopirox (CPX), a synthetic,
broad-spectrum antifungal agent with antibacterial, anti-inflammatory and potential
antineoplastic activities. Upon intravenous administration of fosciclopirox, the POM
moiety is cleaved off by phosphatases and the active metabolite CPX is released. Although
its exact anticancer mechanism is not yet fully elucidated, CPX has been shown to
inhibit tumor cell proliferation, induce apoptosis, and reduce tumor cell mobility
in certain cancer types. CPX inhibits Notch1 activation and inhibits the Notch1-mediated
signaling pathway, which is upregulated in many cancer cell types. This inhibits Notch
downstream target proteins, inhibits the expression of gamma-secretase complex proteins,
and prevents proliferation in susceptible cancer cells. CPX inhibits the iron-containing
enzymes, catalase and peroxidase, which facilitate the decomposition of hydrogen peroxide,
a reactive oxygen species (ROS) involved in oxidative stress. CPX also inhibits the
iron-dependent enzyme ribonucleotide reductase, which is essential in DNA synthesis.
CPX downregulates protein expression of cyclin D1 and cyclin E1, as well as their
enzymatic counterparts cyclin-dependent kinases 4 and 2 (CDK4 and CDK2), which may
inhibit tumor cell proliferation by slowing cell cycle progression from G1/G0 to S
phase. Further, CPX may induce apoptosis by downregulating the expression of anti-apoptotic
proteins, Bcl-xL and survivin, and increasing cleavage of Bcl-2. Additionally, CPX
may inhibit tumor cell proliferation, survival and motility by inhibiting the phosphorylation
of p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1),
two downstream effector molecules of the mammalian target of rapamycin complex 1 (mTORC1).
The CPX-POM prodrug improves the solubility of CPX and increases systemic efficacy.;
UNII : G8FR269QPQ;
InChIKey : NTKBXPWLNROYPE-UHFFFAOYSA-N;
CAS number : 1380539-06-9;
Molecule name : CPX POM; CPX-POM;
NCI Metathesaurus CUI : CL562696;
Origin ID : C175786;
UMLS CUI : C4733643;
Currated CISMeF NLP mapping
- Semantic type(s)
- concept_is_in_subset
