Synthesis of a thiophene-based fluorinated library applied to fragment-based drug discovery via19F NMR with confirmed binding to mutant HRASG12V
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Synthesis of a thiophene-based fluorinated library applied to fragment-based drug discovery via19F NMR with confirmed binding to mutant HRASG12V
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10406 - Analytical chemistry
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
New journal of chemistry
ISSN
1144-0546
e-ISSN
1369-9261
Volume of the periodical
48
Issue of the periodical within the volume
41
Country of publishing house
GB - UNITED KINGDOM
Number of pages
6
Pages from-to
17872-17877
UT code for WoS article
001330741600001
EID of the result in the Scopus database
2-s2.0-85206660457