Linked Life Data

20890793

Source:http://linkedlifedata.com/resource/pubmed/id/20890793

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-11-5
pubmed:abstractText
Activating mutations of KIT play an important role in the pathophysiology of several human malignancies, including acute myeloid leukemia. Activated KIT kinase is therefore a promising molecular target for the treatment of many malignancies harboring KIT activation. Here we examined the potency of a novel KIT inhibitor KI-328 against different types of mutant KIT kinases recurrently identified in AML. KI-328 shows selective potency against KIT kinase for the in vitro kinase assay, and inhibits the growth of wild-type (Wt)- and mutant-KIT-expressing cells, while it has little potency against D816V-KIT. Comparable analysis of several potent KIT inhibitors regarding growth inhibitory effects on a variety of mutant-KIT-expressing cells revealed that multi-kinase inhibitors have the same potency against D816V-KIT as other mutant KITs; however, the predominant potency against D816V-KIT was observed in heat shock protein 90 (HSP90) inhibitors. Furthermore, HSP90 inhibitors suppress the growth of D816V-KIT-expressing cells at the concentration at which the growth of other mutant-KIT-expressing cells is not affected. These results collectively indicated that potent KIT inhibitors have different potency against the type of mutant KIT kinases. Therefore, KIT inhibitors are required to validate potency against several types of mutant KIT kinases for the clinical development.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1865-3774
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
624-33
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Selective KIT inhibitor KI-328 and HSP90 inhibitor show different potency against the type of KIT mutations recurrently identified in acute myeloid leukemia.
pubmed:affiliation
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't