Novel Imatinib Derivatives with Altered Specificity between Bcr-AbI and FMS, KIT, and PDGF Receptors (Journal article)

Skobridis, K./ Kinigopoulou, M./ Theodorou, V./ Giannousi, E./ Russell, A./ Chauhan, R./ Sala, R./ Brownlow, N./ Kiriakidis, S./ Domin, J./ Tzakos, A. G./ Dibb, N. J.

Imatinib is a clinically important ATP analogue inhibitor that targets the tyrosine kinase domain of the intracellular AbI kinase and the PDGF receptor family. Imatinib has revolutionised the treatment of chronic myeloid leukaemia, which is caused by the oncogene Bcr-AbI and certain solid tumours that harbor oncogenic mutations of the PDGF receptor family. As a leading kinase inhibitor, imatinib also provides an excellent model system to investigate how changes in drug design impact biological activity, which is an important consideration for rational drug design. Herein we report a new series of imatinib derivatives that in general have greater activity against the family of PDGF receptors and poorer activity against AbI, as a result of modifications of the phenyl and N-methylpiperazine rings. These new compounds provide a platform for further drug development against the therapeutically important PDGF receptor family and they also provide insight into the engineering of drugs with altered biological activity.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας
Keywords: drug design,imatinib,kinase inhibitors,oncogenes,synthesis,chronic myeloid-leukemia,phenylamino-pyrimidine pap,kinase inhibitor sti571,tyrosine kinase,c-kit,philadelphia-chromosome,activating mutations,sti-571 inhibition,crystal-structure,structural basis
ISSN: 1860-7179
Link: <Go to ISI>://000273725700014
Publisher: Wiley-VCH Verlag
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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