Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

FB2 is a novel Abl/Src dual tyrosine kinase inhibitor which is designed to overcome imatinib resistance. Besides imatinib-sensitive cell lines (K562), FB2 significantly inhibited the growth of imatinib-resistant cell lines of different resistance mechanisms (K562/G5.0 and K562/G01), and decreased the expression of autophosphorylation of Bcr/Abl, c-Src and Lyn kinases on them. It also inhibited the proliferation of Src over activated cells DU145 and MDA-MB-231. Furthermore, FB2 potently prolonged the survival time of non-obese diabetic/severe combined immunodeficient mice harboured K562/G5.0 cells. These results indicated that FB2, an Abl/Src dual tyrosine kinase inhibitor, is a promising candidate for imatinib-resistant CML and Src over activated cancer.
 ...
PMID:Activity of FB2, a novel dual Abl/Src tyrosine kinase inhibitor, against imatinib-resistant chronic myeloid leukemia in vivo and in vitro. 1934 30

We have previously shown the inhibition of the small-molecule inhibitor FB2 on imatinib-sensitive and resistance CML cell lines with the wild-type Bcr-Abl fusion gene. Here we report the potent and selective antiproliferation on FB2 on transfected Ba/F3 p210 cell lines expressing various isoforms of Bcr-Abl (wild-type, Y253F, T315I). FB2 which orients Bcr-Abl and Src kinase activities, is shown to override imatinib-resistance CML involving Y253F mutation in the Abl kinase domain of the fusion protein except T315I in vivo and in vitro. Thus, we present FB2 that displays potency toward Bcr-Abl and Src as the molecular target, and which could potentially be used to override drug resistance in CML.
 ...
PMID:Activity of the potent dual Abl/Src tyrosine kinase inhibitor FB2 against Bcr-Abl positive cell lines in vitro and in vivo. 2073 63