Synthesis of a thiophene-based fluorinated library applied to fragment-based drug discovery via19F NMR with confirmed binding to mutant HRASG12V

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F24%3A50021774" target="_blank" >RIV/62690094:18470/24:50021774 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.rsc.org/en/content/articlelanding/2024/nj/d4nj00727a" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2024/nj/d4nj00727a</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d4nj00727a" target="_blank" >10.1039/d4nj00727a</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis of a thiophene-based fluorinated library applied to fragment-based drug discovery via19F NMR with confirmed binding to mutant HRASG12V

Popis výsledku v původním jazyce

Thiophene containing drugs have been developed and show up among many important drugs currently in the market, like Plavix (R), Cymbalta (R) and Tomudex (R). However, this important organic group is still not present in the fluorine fragment libraries found in the literature. To fix this and contribute to increasing the structural diversity of fragment libraries, we synthesized a fluorinated, bicyclic, thiophene-based fragment library in a modular fashion to be screened via ligand observed F-19 NMR against drug targets. For certain compounds in the synthesized library, binding was detected against the HRAS mutant G12V, a notoriously undruggable cancer target, and further confirmed with N-15 HSQC NMR experiments. To exclude the possibility that the binding was promiscuous, the best binding fragment was screened against an unrelated protein, RNase 5 and was shown to be a non-binder.

Název v anglickém jazyce

Synthesis of a thiophene-based fluorinated library applied to fragment-based drug discovery via19F NMR with confirmed binding to mutant HRASG12V

Popis výsledku anglicky

Thiophene containing drugs have been developed and show up among many important drugs currently in the market, like Plavix (R), Cymbalta (R) and Tomudex (R). However, this important organic group is still not present in the fluorine fragment libraries found in the literature. To fix this and contribute to increasing the structural diversity of fragment libraries, we synthesized a fluorinated, bicyclic, thiophene-based fragment library in a modular fashion to be screened via ligand observed F-19 NMR against drug targets. For certain compounds in the synthesized library, binding was detected against the HRAS mutant G12V, a notoriously undruggable cancer target, and further confirmed with N-15 HSQC NMR experiments. To exclude the possibility that the binding was promiscuous, the best binding fragment was screened against an unrelated protein, RNase 5 and was shown to be a non-binder.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10406 - Analytical chemistry

Projekt

—

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

New journal of chemistry

ISSN

1144-0546

e-ISSN

1369-9261

Svazek periodika

48

Číslo periodika v rámci svazku

41

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

6

Strana od-do

17872-17877

Kód UT WoS článku

001330741600001

EID výsledku v databázi Scopus

2-s2.0-85206660457