About: The new platinum(IV) derivative LA-12 shows stronger inhibitory effect on Hsp90 function compared to cisplatin     Goto   Sponge   NotDistinct   Permalink

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  • Cisplatin and its derivatives are commonly used anti-cancer drugs. However, cisplatin has clinical limitations as serious side effects and frequent emergence of resistance. LA-12 shows increased intracellular penetration resulting in improved cytotoxicity in cancer cell lines, including cisplatin resistant cells. LA-12 disrupts cellular proliferation regardless of p53 status, however the potency of the drug is greatly enhanced by the presence of functional p53. Binding of LA-12 to Hsp90 was demonstrated and an inhibitory effect on Hsp90 chaperoning function was shown by decrease of Hsp90-assisted wild-type p53 binding to p21WAF1 promoter sequence in vitro and by accelerated ubiqutination and degradation of primarily unfolded mutant p53 proteins. LA-12 induced degradation of Hsp90 client proteins (Cyclin D1 and estrogen receptor) was shown and proved as more efficient compared to cisplatin.
  • Cisplatin and its derivatives are commonly used anti-cancer drugs. However, cisplatin has clinical limitations as serious side effects and frequent emergence of resistance. LA-12 shows increased intracellular penetration resulting in improved cytotoxicity in cancer cell lines, including cisplatin resistant cells. LA-12 disrupts cellular proliferation regardless of p53 status, however the potency of the drug is greatly enhanced by the presence of functional p53. Binding of LA-12 to Hsp90 was demonstrated and an inhibitory effect on Hsp90 chaperoning function was shown by decrease of Hsp90-assisted wild-type p53 binding to p21WAF1 promoter sequence in vitro and by accelerated ubiqutination and degradation of primarily unfolded mutant p53 proteins. LA-12 induced degradation of Hsp90 client proteins (Cyclin D1 and estrogen receptor) was shown and proved as more efficient compared to cisplatin. (en)
Title
  • The new platinum(IV) derivative LA-12 shows stronger inhibitory effect on Hsp90 function compared to cisplatin
  • The new platinum(IV) derivative LA-12 shows stronger inhibitory effect on Hsp90 function compared to cisplatin (en)
skos:prefLabel
  • The new platinum(IV) derivative LA-12 shows stronger inhibitory effect on Hsp90 function compared to cisplatin
  • The new platinum(IV) derivative LA-12 shows stronger inhibitory effect on Hsp90 function compared to cisplatin (en)
skos:notation
  • RIV/00209805:_____/10:#0000115!RIV11-MZ0-00209805
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • P(NS9812), Z(MZ0MOU2005)
http://linked.open...iv/cisloPeriodika
  • 15.6.2010
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 274738
http://linked.open...ai/riv/idVysledku
  • RIV/00209805:_____/10:#0000115
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • LA-12, cisplatin, Hsp90 (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV
  • [4C5D7D1A9DEC]
http://linked.open...i/riv/nazevZdroje
  • Molecular cancer
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 9
http://linked.open...iv/tvurceVysledku
  • Hrstka, Roman
  • Kvardová, Veronika
  • Vojtěšek, Bořivoj
  • Müller, Petr
  • Matoulková, Eva
http://linked.open...ain/vavai/riv/wos
  • 000279281100001
http://linked.open...n/vavai/riv/zamer
issn
  • 1476-4598
number of pages
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