ARRY-520, a novel KSP inhibitor with potent activity in hematological and taxane-resistant tumor models.
Anticancer Res
; 29(11): 4373-80, 2009 Nov.
Article
em En
| MEDLINE
| ID: mdl-20032381
ABSTRACT
AIM:
Profiling the efficacy and pharmacodynamic activity of the kinesin spindle protein (KSP) inhibitor ARRY-520 will aid the identification of responsive tumor types and pharmacodynamic profiles that correlate with activity. MATERIALS ANDMETHODS:
In vivo activity was evaluated in a diverse panel of 16 different tumor xenograft models. Pharmacodynamic activity was evaluated in selected models.RESULTS:
ARRY-520 had low nanomolar antiproliferative activity in tumor cell lines. Monopolar spindles were formed at active potencies. Partial or complete responses were observed in 13/16 xenograft models. Hematological tumors were particularly sensitive, with a 100% complete response rate in some models. Maintenance of mitotic block for a sufficient length of time for cells to lose survival signals and progress to apoptosis was a key component of the mechanism of activity. ARRY-520 was also active in several taxane resistant models.CONCLUSION:
The data provide a rationale for clinical evaluation of the activity of ARRY-520 in hematological carcinomas and taxane-resistant tumors.
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Base de dados:
MEDLINE
Assunto principal:
Tiadiazóis
/
Cinesinas
/
Taxoides
/
Neoplasias
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article