Structure-activity relationship study of small-molecule inhibitor of Atg12-Atg3 protein-protein interaction

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00598057" target="_blank" >RIV/61388963:_____/24:00598057 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60461373:22330/24:43929822

Výsledek na webu

<a href="https://doi.org/10.1016/j.bmcl.2024.129939" target="_blank" >https://doi.org/10.1016/j.bmcl.2024.129939</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmcl.2024.129939" target="_blank" >10.1016/j.bmcl.2024.129939</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Structure-activity relationship study of small-molecule inhibitor of Atg12-Atg3 protein-protein interaction

Popis výsledku v původním jazyce

Autophagy is a catabolic process that was described to play a critical role in advanced stages of cancer, wherein it maintains tumor cell homeostasis and growth by supplying nutrients. Autophagy is also described to support alternative cellular trafficking pathways, providing a non-canonical autophagy-dependent inflammatory cytokine secretion mechanism. Therefore, autophagy inhibitors have high potential in the treatment of cancer and acute inflammation. In our study, we identified compound 1 as an inhibitor of the ATG12-ATG3 protein-protein interaction. We focused on the systematic modification of the original hit 1, a casein kinase 2 (CK2) inhibitor, to find potent disruptors of ATG12-ATG3 protein-protein interaction. A systematic modification of the hit structure led us to a wide plethora of compounds that maintain its ATG12-ATG3 inhibitory activity, which could act as a viable starting point to design new compounds with diverse therapeutic applications.

Název v anglickém jazyce

Structure-activity relationship study of small-molecule inhibitor of Atg12-Atg3 protein-protein interaction

Popis výsledku anglicky

Autophagy is a catabolic process that was described to play a critical role in advanced stages of cancer, wherein it maintains tumor cell homeostasis and growth by supplying nutrients. Autophagy is also described to support alternative cellular trafficking pathways, providing a non-canonical autophagy-dependent inflammatory cytokine secretion mechanism. Therefore, autophagy inhibitors have high potential in the treatment of cancer and acute inflammation. In our study, we identified compound 1 as an inhibitor of the ATG12-ATG3 protein-protein interaction. We focused on the systematic modification of the original hit 1, a casein kinase 2 (CK2) inhibitor, to find potent disruptors of ATG12-ATG3 protein-protein interaction. A systematic modification of the hit structure led us to a wide plethora of compounds that maintain its ATG12-ATG3 inhibitory activity, which could act as a viable starting point to design new compounds with diverse therapeutic applications.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/EH22_008%2F0004607" target="_blank" >EH22_008/0004607: Nové technologie pro translační výzkum ve farmaceutických vědách /NETPHARM</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Bioorganic and Medicinal Chemistry Letters

ISSN

0960-894X

e-ISSN

1464-3405

Svazek periodika

112

Číslo periodika v rámci svazku

November

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

6

Strana od-do

129939

Kód UT WoS článku

001309826500001

EID výsledku v databázi Scopus

2-s2.0-85203245928