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

Result code in 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>
Result on the web
<a href="https://hdl.handle.net/11104/0375609" target="_blank" >https://hdl.handle.net/11104/0375609</a>
DOI - Digital Object Identifier
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Result language
angličtina
Original language name
Purine Nucleoside Phosphorylase Inhibitors: A replacement of 9-deazapurine for pyrrole
Original language description
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.
Czech name
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Czech description
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Project
<a href="/en/project/TN02000109" target="_blank" >TN02000109: Personalised Medicine: From Translational Research into Biomedical Applications</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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