Metallacarborane Sulfamides: Unconventional, Specific, and Highly Selective Inhibitors of Carbonic Anhydrase IX

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00511423" target="_blank" >RIV/61388963:_____/19:00511423 - isvavai.cz</a>
Alternative codes found
RIV/61388980:_____/19:00511473 RIV/68378050:_____/19:00511473 RIV/61989592:15110/19:73598969 RIV/00216208:11310/19:10401472
Result on the web
<a href="https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.9b00945" target="_blank" >https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.9b00945</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jmedchem.9b00945" target="_blank" >10.1021/acs.jmedchem.9b00945</a>

Result language
angličtina
Original language name
Metallacarborane Sulfamides: Unconventional, Specific, and Highly Selective Inhibitors of Carbonic Anhydrase IX
Original language description
Carbonic anhydrase IX (CAIX) is a transmembrane enzyme that regulates pH in hypoxic tumors and promotes tumor cell survival. Its expression is associated with the occurrence of metastases and poor prognosis. Here, we present nine derivatives of the cobalt bis(dicarbollide)(1−) anion substituted at the boron or carbon sites by alkysulfamide group(s) as highly specific and selective inhibitors of CAIX. Interactions of these compounds with the active site of CAIX were explored on the atomic level using protein crystallography. Two selected derivatives display subnanomolar or picomolar inhibition constants and high selectivity for the tumor-specific CAIX over cytosolic isoform CAII. Both derivatives had a time-dependent effect on the growth of multicellular spheroids of HT-29 and HCT116 colorectal cancer cells, facilitated penetration and/or accumulation of doxorubicin into spheroids, and displayed low toxicity and showed promising pharmacokinetics and a significant inhibitory effect on tumor growth in syngenic breast 4T1 and colorectal HT-29 cancer xenotransplants.
Czech name
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Czech description
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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
10608 - Biochemistry and molecular biology

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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