Latest research on Imatinib

Imatinib is a small molecule kinase inhibitor used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec (USA) or Glivec (Europe/Australia) as its mesylate salt, imatinib mesilate (INN). It is occasionally referred to as CGP57148B or STI571 (especially in older publications). It is used in treating chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs) and a number of other malignancies. It is the first member of a new class of agents that act by inhibiting particular tyrosine kinase enzymes, instead of non-specifically inhibiting rapidly dividing cells.

Latest findings

Our results also indicate a role for adjuvant treatment with Imatinib, which is currently being investigated in prospective randomised clinical trials. [source, 2003]
The unprecedented success of the BCR/ABL TYROSINE kinase inhibitor Imatinib (STI571/Gleevec, Novartis) in the treatment of chronic myeloid leukemia (CML) has inspired great expectations for this approach (1, 2). [source, 2003]
Complete hematologic responses to Imatinib are seen in >95% of CML patients and a major cytogenetic response in >60% of patients treated in the chronic phase of the disease (3, 4). [source, 2003]
In fact, virtually all patients with advanced stages of CML ultimately manifest Imatinib resistance (5-7), and it is expected that other protein targets will evolve drug resistant forms as well in response to therapy. [source, 2003]
In previous work, we reported the results of a screen involving random mutagenesis of BCR/ABL to reveal the spectrum of mutations conferring resistance to Imatinib. [source, 2003]
Following an incubation of 14-16 hr at 37°C, 5% CO2, selection for Imatinib resistant cells was initiated by removal of IL-3 from the medium by washing the cells in WEHI-3B free RPMI/10% FCS. [source, 2003]
More specifically, 8 x 106 cells were mixed with 28.8 ml RPMI, 9.6 ml FCS, 9.6 ml of 1.2% Bacto-agar (made in PBS, autoclaved and cooled to 42°C), and supplemented with concentrations of 5 - 10 mM Imatinib. [source, 2003]
The mix was then plated, 3 ml/well, into 6-well plates and incubated at 37°C, 5% CO2, for 10 days before single colonies were picked and expanded separately in 3 ml RPMI/10% FCS in the presence of 5 - 10 mM Imatinib. Following expansion, genomic DNA was isolated using the Qiagen DNeasy Kit and sequenced. [source, 2003]
Imatinib was added to the media in increasing concentrations (final concentration: 0, 1, 3, 5, 10, and 20 mM) across the plate and cells incubated for 60 hr. [source, 2003]
All assays were performed in quadruplicate and readings averaged and plotted against Imatinib concentration as a best fit sigmoidal curve by using a nonlinear curve-fitting algorithm (Origin 7.0, Origin Lab, Northhampton, MA). The drug concentration resulting in 50% cell viability was scored as the Cellular IC50. [source, 2003]