Haematologica Reports 2005; 1(issue 8):
20-27[prev][index][next]
Imatinib – an overview
Deininger MWN
Oregon Health & Science University, Center for Hematologic
Malignancies, Portland, OR, USA
Historical perspective and chemical
development
The potential of Abl kinase inhibitors for the treatment of
Abl-related leukemias was suggested as early as 1989.1
Several tyrphostins, a series of compounds derived from the
erbstatin, an inhibitor of the epidermal growth factor receptor
were shown to be potent and rather specific inhibitors of Bcr-Abl,
with biological activity in cell lines derived from patients with
chronic myeloid leukemia (CML).2 Tyrphostins were
however not developed clinically. Imatinib, the first clinically
viable Abl kinase inhibitor, is the result of a medicinal chemistry
project initiated by Ciba Geigy (now Novartis) in the early 1990s,
with protein kinase C as the initial target. During this project, a
2-phenylaminopyrimidine derivative was identified as the lead
compound.3,4 [>Read full article in
PDF]
