Biology and therapeutic applications of the proton-coupled folate transporter.
antifolate
folate
hereditary folate malabsorption
one-carbon
proton-coupled folate transporter
purine
Journal
Expert opinion on drug metabolism & toxicology
ISSN: 1744-7607
Titre abrégé: Expert Opin Drug Metab Toxicol
Pays: England
ID NLM: 101228422
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
pubmed:
15
10
2022
medline:
8
11
2022
entrez:
14
10
2022
Statut:
ppublish
Résumé
The proton-coupled folate transporter (PCFT; SLC46A1) was discovered in 2006 as the principal mechanism by which folates are absorbed in the intestine and the causal basis for hereditary folate malabsorption (HFM). In 2011, it was found that PCFT is highly expressed in many tumors. This stimulated interest in using PCFT for cytotoxic drug targeting, taking advantage of the substantial levels of PCFT transport and acidic pH conditions commonly associated with tumors. We summarize the literature from 2006 to 2022 that explores the role of PCFT in the intestinal absorption of dietary folates and its role in HFM and as a transporter of folates and antifolates such as pemetrexed (Alimta) in relation to cancer. We provide the rationale for the discovery of a new generation of targeted pyrrolo[2,3- We summarize the promising future and potential challenges of implementing PCFT-targeted therapeutics for HFM and a variety of cancers.
Identifiants
pubmed: 36239195
doi: 10.1080/17425255.2022.2136071
pmc: PMC9637735
mid: NIHMS1845542
doi:
Substances chimiques
Proton-Coupled Folate Transporter
0
Folic Acid Antagonists
0
Pemetrexed
04Q9AIZ7NO
Antineoplastic Agents
0
Folic Acid
935E97BOY8
SLC46A1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
695-706Subventions
Organisme : NCI NIH HHS
ID : R01 CA053535
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA250469
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009531
Pays : United States
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