How selective are clinical CDK4/6 inhibitors?
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F21%3A73610841" target="_blank" >RIV/61989592:15310/21:73610841 - isvavai.cz</a>
Výsledek na webu
<a href="https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.21769" target="_blank" >https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.21769</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/med.21769" target="_blank" >10.1002/med.21769</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
How selective are clinical CDK4/6 inhibitors?
Popis výsledku v původním jazyce
Pharmacological inhibition of cyclin-dependent kinase 4/6 (CDK4/6) has emerged as an efficient approach for treating breast cancer, and its clinical potential is expanding to other cancers. CDK4/6 inhibitors were originally believed to act by arresting proliferation in the G1 phase, but it is gradually becoming clear that the cellular response to these compounds is far more complex than this. Multiple context-dependent mechanisms of action are emerging, involving modulation of quiescence, senescence, autophagy, cellular metabolism, and enhanced tumor cell immunogenicity. These mechanisms may be driven by interactions with unexpected targets. We review cellular responses to the Food and Drug Administration-approved CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib, and summarize available knowledge of other drugs undergoing clinical trials, including data on their off-target landscapes. We emphasize the importance of comprehensively characterizing drugs' selectivity profiles to maximize their clinical efficacy and safety and to facilitate their repurposing to treat additional diseases based on their target spectrum.
Název v anglickém jazyce
How selective are clinical CDK4/6 inhibitors?
Popis výsledku anglicky
Pharmacological inhibition of cyclin-dependent kinase 4/6 (CDK4/6) has emerged as an efficient approach for treating breast cancer, and its clinical potential is expanding to other cancers. CDK4/6 inhibitors were originally believed to act by arresting proliferation in the G1 phase, but it is gradually becoming clear that the cellular response to these compounds is far more complex than this. Multiple context-dependent mechanisms of action are emerging, involving modulation of quiescence, senescence, autophagy, cellular metabolism, and enhanced tumor cell immunogenicity. These mechanisms may be driven by interactions with unexpected targets. We review cellular responses to the Food and Drug Administration-approved CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib, and summarize available knowledge of other drugs undergoing clinical trials, including data on their off-target landscapes. We emphasize the importance of comprehensively characterizing drugs' selectivity profiles to maximize their clinical efficacy and safety and to facilitate their repurposing to treat additional diseases based on their target spectrum.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30107 - Medicinal chemistry
Návaznosti výsledku
Projekt
<a href="/cs/project/GA19-08410S" target="_blank" >GA19-08410S: Substituované imidazopyrimidiny: Racionální návrh a vývoj specifických inhibitorů proteinkinas s protinádorovým účinkem</a><br>
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2021
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
MEDICINAL RESEARCH REVIEWS
ISSN
0198-6325
e-ISSN
—
Svazek periodika
41
Číslo periodika v rámci svazku
3
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
21
Strana od-do
1578-1598
Kód UT WoS článku
000597659000001
EID výsledku v databázi Scopus
2-s2.0-85097383005