mTORC1 signalling is inhibited by rapamycin and its analogues, though these compounds act allosterically, in the place of directly suppressing mTOR AG-1478 solubility kinase activity. Rapamycin and its analogues have been proven to be cytostatic, maybe not cytotoxic, to leukemic and other cancer cells. Given the significance of the PI3K/Akt/mTOR process in regulating mRNA translation of genes that encode for professional oncogenic proteins and activated mTORC1 signalling in a high percentage of cancers, these kinases have been earnestly pursued as oncology drug targets. A number of pharmacological inhibitors have been recognized, a few of which have reached advanced level clinical stages. But, it has recently become clear that the mTOR pathway participates in a complicated feedback loop that can impair activation of Akt. It’s been proven that continuous treatment of cancer cells or individuals with mTOR inhibitors causes improved PI3K action that leads to phosphorylation of Akt and eIF4E, and promotes cancer Neuroblastoma cell survival. eIF4E, operating downstream of Akt and mTOR, recapitulates Akts activity in tumourigenesis and drug resistance, and Akt signalling via eIF4E is definitely an important process of oncogenesis and drug resistance in vivo. For these reasons, dual targeting of both mTOR and Akt, or directly inhibiting eIF4E action, have already been proposed as treatments for cancer. As well as the PI3K/Akt/mTOR pathway, eIF4E can also be the target of the Ras/Raf/MAP signalling cascade which can be activated by growth factors and for the strain activated p38 MAP kinase pathway. Erk1/2 and p38 then phosphorylate MAP kinase connecting kinase 1 and Mnk2. MAPK inhibitors The Erk pathway can be stimulated in several cancers, showing, for example, activating mutations in Ras or loss of function of the Ras GTPase activator protein NF1. Mnk1 and Mnk2 specifically phosphorylate serine 209 of eIF4E inside the eIF4F complex, by virtue of the interaction between the Mnks and eIF4E, which serves to recruit Mnks to act on eIF4E. Mnk1 and Mnk2 knock out or knock in mice, where Ser209 was replaced by alanine, showed no eIF4E phosphorylation and considerably attenuated tumour growth. Somewhat, while Mnk action is essential for eIF4E mediated oncogenic change, it is dispensable for normal growth. Pharmacologically suppressing Mnks might, therefore, provide a stylish therapeutic technique for cancer. Despite improved understanding of structure and function of the Mnks, little progress continues to be created using Mnk targeted drug discovery. In this review we want to update the progress made in validating the Mnks as a possible therapeutic target and to supply an insight into binding models of selected prototype inhibitors in complex together with the Mnks. The rationales and inhibitor design rules is likely to be discussed.