Disease associated mutations at valine 804 in the RET receptor tyrosine kinase confer resistance to selective kinase inhibitors (Articolo in rivista)

Type

• Prodotto della ricerca (Classe)
• Articolo in rivista (Classe)

Label

• Disease associated mutations at valine 804 in the RET receptor tyrosine kinase confer resistance to selective kinase inhibitors (Articolo in rivista) (literal)

Anno

• 2004-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

• 10.1038/sj.onc.1207810 (literal)

Alternative label

• Carlomagno F; Guida T; Anaganti S; Vecchio G; Fusco A; Ryan AJ; Billaud M; Santoro M, (2004)
  Disease associated mutations at valine 804 in the RET receptor tyrosine kinase confer resistance to selective kinase inhibitors
  in Oncogene (Basingstoke)
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Carlomagno F; Guida T; Anaganti S; Vecchio G; Fusco A; Ryan AJ; Billaud M; Santoro M, (literal)

Pagina inizio

• 6056 (literal)

Pagina fine

• 6063 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 23 (literal)

Rivista

• Oncogene (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali

• 8 (literal)

Note

• ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Dipartimento di Biologia e Patologia Cellulare e Molecolare, University 'Federico II', c/o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, via S. Pansini 5, Napoli, Italia; Cancer Discovery, Astra Zeneca Mereside, Alderley Park, Macclesfield, Cheshire, UK; Laboratoire de Genetique, CNRS, Lyon, France (literal)

Titolo

• Disease associated mutations at valine 804 in the RET receptor tyrosine kinase confer resistance to selective kinase inhibitors (literal)

Abstract

• We have recently demonstrated that the pyrazolopyrimidines PP1and PP2 and the 4-anilinoquinazoline ZD6474 display a strong inhibitory activity (IC50p100 nM) towards constitutively active oncogenic RET kinases. Here, we show that most oncogenic MEN2-associated RET kinase mutants are highly susceptible to PP1, PP2 and ZD6474 inhibition. In contrast, MEN2-associated swap of bulky hydrophobic leucine or methionine residues for valine 804 in the RET kinase domain causes resistance to the three compounds. Substitution of valine 804 with the small amino- acid glycine renders the RET kinase even more susceptible to inhibition (ZD6474 IC50: 20nM) than the wild-type kinase. Our data identify valine 804 of RET as a structural determinant mediating resistance to pyrazolopyrimidines and 4-anilinoquinazolines. (literal)

Prodotto di

• Institute Experimental Endocrinology and Oncology \"Gaetano Salvatore\" (IEOS) (Istituto)

Autore CNR

• MASSIMO SANTORO (Unità di personale esterno)

Incoming links:

Prodotto

• Institute Experimental Endocrinology and Oncology \"Gaetano Salvatore\" (IEOS) (Istituto)

Autore CNR di

• MASSIMO SANTORO (Unità di personale esterno)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Oncogene (Rivista)