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Literature summary for 4.98.1.1 extracted from

  • Mansi, M.; Howley, R.; Chen, B.
    Methods to measure the inhibition of ABCG2 transporter and ferrochelatase activity to enhance aminolevulinic acid-protoporphyrin IX fluorescence-guided tumor detection and resection (2022), Methods Mol. Biol., 2394, 823-835.
    View publication on PubMed
Search for more literature for 4.98.1.1

Application

Application Comment Organism
analysis inhibition of ABCG2 transporter and ferrochelatase activity to enhance aminolevulinic acid-protoporphyrin IX fluorescence-guided tumor detection and resection. Aminolevulinic acid (ALA) has been clinically used as an intraoperative fluorescence probe for protoporphyrin IX (PpIX) fluorescence-guided tumor resection and a PDT agent for cancer treatment. Although tumor tissues often show increased ALA-PpIX fluorescence compared with normal tissues, which enables the use of ALA for tumor imaging and targeting, weak tumor PpIX fluorescence as well as the heterogeneity in tumor fluorescence severely limit its clinical application. Intracellular PpIX in tumor cells is reduced by two major mechanisms, efflux by ATP-binding cassette (ABC) transporters such as ABCG2 and bioconversion to form heme by ferrochelatase (FECH) in the heme biosynthesis pathway. Targeting these two predominant PpIX-reducing mechanisms for the enhancement of ALA-PpIX have yielded a plethora of promising results and stimulated the clinical exploration of these enhancement strategies. Development of ABCG2 and FECH inhibitors and rational use of these inhibitors to optimize ALA-based tumor detection and treatment Homo sapiens
drug development inhibition of ABCG2 transporter and ferrochelatase activity to enhance aminolevulinic acid-protoporphyrin IX fluorescence-guided tumor detection and resection. Aminolevulinic acid (ALA) has been clinically used as an intraoperative fluorescence probe for protoporphyrin IX (PpIX) fluorescence-guided tumor resection and a PDT agent for cancer treatment. Although tumor tissues often show increased ALA-PpIX fluorescence compared with normal tissues, which enables the use of ALA for tumor imaging and targeting, weak tumor PpIX fluorescence as well as the heterogeneity in tumor fluorescence severely limit its clinical application. Intracellular PpIX in tumor cells is reduced by two major mechanisms, efflux by ATP-binding cassette (ABC) transporters such as ABCG2 and bioconversion to form heme by ferrochelatase (FECH) in the heme biosynthesis pathway. Targeting these two predominant PpIX-reducing mechanisms for the enhancement of ALA-PpIX have yielded a plethora of promising results and stimulated the clinical exploration of these enhancement strategies. Development of ABCG2 and FECH inhibitors and rational use of these inhibitors to optimize ALA-based tumor detection and treatment Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
EDTA
-
 Homo sapiens
N-methyl mesoporphyrin IX NMMP Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens FECH can also catalyze the chelation between zinc and PpIX to produce zinc protoporphyrin IX (Zn-PpIX). FECH activity is estimated by the production of Zn-PpIX following the incubation of cell lysates with PpIX and zinc acetate ?
-
-
protoporphyrin IX + Fe2+ Homo sapiens
-
 protoheme + 2 H+
-
 ?
protoporphyrin IX + Zn2+ Homo sapiens
-
 Zn-protoporphyrin IX + 2 H+
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q53FU1
-
-

Source Tissue

Source Tissue Comment Organism Textmining
carcinoma cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information FECH can also catalyze the chelation between zinc and PpIX to produce zinc protoporphyrin IX (Zn-PpIX). FECH activity is estimated by the production of Zn-PpIX following the incubation of cell lysates with PpIX and zinc acetate Homo sapiens ?
-
-
additional information FECH can also catalyze the chelation between zinc and PpIX to produce zinc protoporphyrin IX (Zn-PpIX) Homo sapiens ?
-
-
protoporphyrin IX + Fe2+
-
 Homo sapiens protoheme + 2 H+
-
 ?
protoporphyrin IX + Zn2+
-
 Homo sapiens Zn-protoporphyrin IX + 2 H+
-
 ?

Synonyms

Synonyms Comment Organism
FeCH
-
 Homo sapiens
ferrochelatase
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
 assay at Homo sapiens

General Information

General Information Comment Organism
malfunction inhibition of ABCG2 transporter and ferrochelatase activity to enhance aminolevulinic acid-protoporphyrin IX fluorescence-guided tumor detection and resection. Evaluation of potential ABCG2 inhibitors for the enhancement of ALA-PpIX in tumor cell lines and inhibition of FECH to enhance ALA-PpIX fluorescence, overview. Inhibition of PpIX bioconversion by pharmacological inhibition of FECH, genetic silencing of FECH or iron chelators significantly increases intracellular PpIX concentration, indicating that blocking the PpIX bioconversion can be explored for enhancing ALA-PpIX fluorescence for tumor detection and targeting Homo sapiens
physiological function aminolevulinic acid (ALA) is an amino acid and has no fluorescence on its own. Once inside cells, it is metabolized in the heme biosynthesis pathway to produce protoporphyrin IX (PpIX), a porphyrin metabolite with fluorescence and photosensitizing property. Intracellular protoporphyrin IX (PpIX) in tumor cells is reduced by two major mechanisms, efflux by ATP-binding cassette (ABC) transporters such as ABCG2 and bioconversion to form heme by ferrochelatase (FECH) in the heme biosynthesis pathway Homo sapiens