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Alzheimer's disease (AD) is a complex neurodegenerative condition with several target proteins contributing to its etiology. With 35.6 million cases worldwide documented in 2011, AD constitutes a devastating health, political, economic, and social problem for all nations. The cases are expected to increase beyond 107 million in 2050; unless an advanced therapy having a capability to delay the disease progression is developed. The curative paradigm of one-compound one-target that has been followed so far has not reached the desired mark. The research focus moved towards single molecule targeting two or more pathogenic mechanisms involved in neuronal death. Over the last few years, medicinal chemists have been paying attention to the design and synthesis of the hybrid molecules that are comprised of two pharmacophores from well-established chemical scaffolds endowed with requisite biological activities in a single entity. The hybrid-based approach has grown to be a central point in the medicinal chemistry field. Various important pharmacophores used for AD have been combined with selected biologically active molecules to get homo- and heterodimers with improved efficacy with additional supplementary actions. This review summarizes the pathogenesis of AD and various progress in the design of hybrid molecules based on the one-compound-various targets paradigm for AD therapy.

JAK2 and JAK3 are non-receptor protein tyrosine kinases implicated in B-cell- and T-cell-mediated diseases. Both enzymes work via different pathways but are involved in the pathogenesis of common lymphoid-derived diseases. Hence, targeting both Janus kinases together can be a potential strategy for the treatment of these diseases. In the present study, two separate pharmacophore-based 3D-QSAR models ADRR.92 (Q(2)(test)0.663, R(2)(train) 0.849, F value 219.3) for JAK2 and ADDRR.142 (Q(2)(test)0.655, R(2)(train) 0.869, F value 206.9) for JAK3 were developed. These models were employed for the screening of a PHASE database of approximately 1.5 million compounds; subsequently, the retrieved hits were screened employing docking simulations with JAK2 and JAK3 proteins. Finally, ADME properties of screened dual inhibitors displaying essential interactions with both proteins were calculated to filter candidates with poor pharmacokinetic profiles. These candidates could serve as novel therapeutic agents in the treatment of lymphoid-related diseases.