Biological and structural investigation of tetrahydro-β-carboline-based selective HDAC6 inhibitors with improved stability
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F24%3A00598294" target="_blank" >RIV/86652036:_____/24:00598294 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0223523424005567?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0223523424005567?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejmech.2024.116676" target="_blank" >10.1016/j.ejmech.2024.116676</a>
Alternative languages
Result language
angličtina
Original language name
Biological and structural investigation of tetrahydro-β-carboline-based selective HDAC6 inhibitors with improved stability
Original language description
Our previously reported HDAC6 inhibitor (HDAC6i) Marbostat-100 (4) 4 ) has provided many arguments for further clinical evaluation. By the substitution of the acidic hydrogen of 4 for different carbon residues, we were able to generate an all-carbon stereocenter, which significantly improves the hydrolytic stability of the inhibitor. Further asymmetric synthesis has shown that the (S) S )-configured inhibitors preferentially bind to HDAC6. This led to the highly selective and potent methyl-substituted derivative S-29b, 29b , which elicited a long-lasting tubulin hyperacetylation in MV4-11 cells. Finally, a crystal structure of the HDAC6/S-29b S- 29b complex provided mechanistic explanation for the high potency and stereoselectivity of synthesized compound series.
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
30107 - Medicinal chemistry
Result continuities
Project
<a href="/en/project/LUAUS23247" target="_blank" >LUAUS23247: Study and development of new epigenetic modulators intended for cancer treatment</a><br>
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
European Journal of Medicinal Chemistry
ISSN
0223-5234
e-ISSN
1768-3254
Volume of the periodical
276
Issue of the periodical within the volume
OCT 5 2024
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
11
Pages from-to
116676
UT code for WoS article
001283375500001
EID of the result in the Scopus database
2-s2.0-85199348983