DEVELOPMENT OF SMALL MOLECULE INHIBITORS OF MNK2

The development of highly selective antineoplastic agents has long been a challenge for the pharmaceutical industry. eIF4E is a general translational factor that is phosphorylated by the Mnk kinases on the Ser209 residue. Elevated levels eIF4E phosphorylation has been linked to the development and survival of several malignant tumours like those of the breast, bladder, prostate, lung, head and neck and glioblastomas. Mnk kinases occur in two isoforms: Mnk1 and Mnk2. Mnk kinases can assume an autoinhibited conformation (DFD-out) in which ATP binding is inhibited. Rapamycin and its analogues were developed to target eIF4E phosphorylation by inhibiting mTOR receptor but were later on found to be ineffective with prolonged use.

Author(s): MARYAM ABBATOR

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