Small molecule inhibitors of DNA-PK for tumor sensitization to anticancer therapy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F17%3A10362727" target="_blank" >RIV/00216208:11150/17:10362727 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.jpp.krakow.pl/journal/archive/06_17/pdf/337_06_17_article.pdf" target="_blank" >http://www.jpp.krakow.pl/journal/archive/06_17/pdf/337_06_17_article.pdf</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Small molecule inhibitors of DNA-PK for tumor sensitization to anticancer therapy

Popis výsledku v původním jazyce

The most sensitive cell structure - a DNA molecule, is the common target of cancer therapy. DNA damage response (controlled by enzymes from the phosphatidylinositol 3-kinase-related kinases family - PIKK) presents many encouraging targets for improving both conventional cytotoxic anticancer therapy and individualized monotherapy. DNA-dependent protein kinase (DNA-PK) is a member of the PIKK superfamily and plays an important role in the detection and repair of DNA double-strand breaks via the non-homologous end-joining pathway. The ability of cancer cells to repair DNA damage is an important element determining their sensitivity to radio-or chemo-therapy. The overactivation of DNA-PK in cancers can result in resistance to anticancer therapy. The inhibition of DNA-PK is a very promising target in anticancer research. However, the specific DNA-PK inhibitors currently known are limited by poor solubility and high metabolic lability in vivo, leading to a short serum half-life. Construction of new compounds based on existing drugs is the most important strategy to improve drug efficacy, pharmacokinetic parameters and to reduce toxicity. This review will describe small molecule inhibitors and summarize their efficacy in synergizing radio-and chemotherapy in vitro.

Název v anglickém jazyce

Small molecule inhibitors of DNA-PK for tumor sensitization to anticancer therapy

Popis výsledku anglicky

The most sensitive cell structure - a DNA molecule, is the common target of cancer therapy. DNA damage response (controlled by enzymes from the phosphatidylinositol 3-kinase-related kinases family - PIKK) presents many encouraging targets for improving both conventional cytotoxic anticancer therapy and individualized monotherapy. DNA-dependent protein kinase (DNA-PK) is a member of the PIKK superfamily and plays an important role in the detection and repair of DNA double-strand breaks via the non-homologous end-joining pathway. The ability of cancer cells to repair DNA damage is an important element determining their sensitivity to radio-or chemo-therapy. The overactivation of DNA-PK in cancers can result in resistance to anticancer therapy. The inhibition of DNA-PK is a very promising target in anticancer research. However, the specific DNA-PK inhibitors currently known are limited by poor solubility and high metabolic lability in vivo, leading to a short serum half-life. Construction of new compounds based on existing drugs is the most important strategy to improve drug efficacy, pharmacokinetic parameters and to reduce toxicity. This review will describe small molecule inhibitors and summarize their efficacy in synergizing radio-and chemotherapy in vitro.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

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Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Physiology and Pharmacology

ISSN

0867-5910

e-ISSN

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Svazek periodika

68

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

PL - Polská republika

Počet stran výsledku

8

Strana od-do

337-344

Kód UT WoS článku

000408565000002

EID výsledku v databázi Scopus

2-s2.0-85027709278