Purine Nucleoside Phosphorylase Inhibitors: A replacement of 9-deazapurine for pyrrole

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00645820" target="_blank" >RIV/61388963:_____/24:00645820 - isvavai.cz</a>

Výsledek na webu

<a href="https://hdl.handle.net/11104/0375609" target="_blank" >https://hdl.handle.net/11104/0375609</a>

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

Purine Nucleoside Phosphorylase Inhibitors: A replacement of 9-deazapurine for pyrrole

Popis výsledku v původním jazyce

Human purine nucleoside phosphorylase (PNP) has been studied for a long time as a suitable target for the treatment of T-cell acute lymphoblastic leukemia (T-ALL). Recently, we have published novel series of very potent human PNP inhibitors based on acyclic nucleoside phosphonates (ANPs) with IC50 values as low as 22 nM (human PNP) and with highly selective toxicity towards various T-lymphoblastic cell lines with CC50 values as low as 9 nm [1]. Unfortunately, the bioavailability in rodent models proved to be poor (below 2%). X-ray crystallography and in silico molecular modeling methods were used to design novel molecules with potentially improved physicochemical profile, where the 9-deaza-6-oxopurine moiety was replaced with pyrrol moiety. Synthesis and biological evaluation of novel PNP inhibitors will be presented.

Název v anglickém jazyce

Purine Nucleoside Phosphorylase Inhibitors: A replacement of 9-deazapurine for pyrrole

Popis výsledku anglicky

Human purine nucleoside phosphorylase (PNP) has been studied for a long time as a suitable target for the treatment of T-cell acute lymphoblastic leukemia (T-ALL). Recently, we have published novel series of very potent human PNP inhibitors based on acyclic nucleoside phosphonates (ANPs) with IC50 values as low as 22 nM (human PNP) and with highly selective toxicity towards various T-lymphoblastic cell lines with CC50 values as low as 9 nm [1]. Unfortunately, the bioavailability in rodent models proved to be poor (below 2%). X-ray crystallography and in silico molecular modeling methods were used to design novel molecules with potentially improved physicochemical profile, where the 9-deaza-6-oxopurine moiety was replaced with pyrrol moiety. Synthesis and biological evaluation of novel PNP inhibitors will be presented.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/TN02000109" target="_blank" >TN02000109: Personalizovaná medicína: Translačním výzkumem k biomedicínským aplikacím</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

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