Aminopeptidase N Inhibitors as Pointers for Overcoming Antitumor Treatment Resistance

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14160%2F22%3A00126601" target="_blank" >RIV/00216224:14160/22:00126601 - isvavai.cz</a>

Result on the web

<a href="https://www.mdpi.com/1422-0067/23/17/9813/htm" target="_blank" >https://www.mdpi.com/1422-0067/23/17/9813/htm</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms23179813" target="_blank" >10.3390/ijms23179813</a>

Result language

angličtina

Original language name

Aminopeptidase N Inhibitors as Pointers for Overcoming Antitumor Treatment Resistance

Original language description

Aminopeptidase N (APN), also known as CD13 antigen or membrane alanyl aminopeptidase, belongs to the M1 family of the MA clan of zinc metallopeptidases. In cancer cells, the inhibition of aminopeptidases including APN causes the phenomenon termed the amino acid deprivation response (AADR), a stress response characterized by the upregulation of amino acid transporters and synthetic enzymes and activation of stress-related pathways such as nuclear factor kB (NFkB) and other pro-apoptotic regulators, which leads to cancer cell death by apoptosis. Recently, APN inhibition has been shown to augment DR4-induced tumor cell death and thus overcome resistance to cancer treatment with DR4-ligand TRAIL, which is available as a recombinant soluble form dulanermin. This implies that APN inhibitors could serve as potential weapons for overcoming cancer treatment resistance. In this study, a series of basically substituted acetamidophenones and the semicarbazones and thiosemicarbazones derived from them were prepared, for which APN inhibitory activity was determined. In addition, a selective anti-proliferative activity against cancer cells expressing APN was demonstrated. Our semicarbazones and thiosemicarbazones are the first compounds of these structural types of Schiff bases that were reported to inhibit not only a zinc-dependent aminopeptidase of the M1 family but also a metalloenzyme.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

—

Continuities

S - Specificky vyzkum na vysokych skolach

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

International Journal of Molecular Sciences

ISSN

1422-0067

e-ISSN

—

Volume of the periodical

23

Issue of the periodical within the volume

17

Country of publishing house

CH - SWITZERLAND

Number of pages

15

Pages from-to

1-15

UT code for WoS article

000851097400001

EID of the result in the Scopus database

2-s2.0-85139557010