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From Single Target to Multitarget/Network Therapeutics in Alzheimer’s Therapy

1
Department of Medicinal Chemistry, Intra-cellular Therapies Inc. 3960 Broadway, New York, NY 10032, USA
2
Department of Organic Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
3
Abital Pharma Pipeline Ltd., Tel Aviv 6789141, Israel
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2014, 7(2), 113-135; https://doi.org/10.3390/ph7020113
Received: 16 December 2013 / Revised: 13 January 2014 / Accepted: 17 January 2014 / Published: 23 January 2014
(This article belongs to the Special Issue CNS-Drugs and Therapy)
Brain network dysfunction in Alzheimer’s disease (AD) involves many proteins (enzymes), processes and pathways, which overlap and influence one another in AD pathogenesis. This complexity challenges the dominant paradigm in drug discovery or a single-target drug for a single mechanism. Although this paradigm has achieved considerable success in some particular diseases, it has failed to provide effective approaches to AD therapy. Network medicines may offer alternative hope for effective treatment of AD and other complex diseases. In contrast to the single-target drug approach, network medicines employ a holistic approach to restore network dysfunction by simultaneously targeting key components in disease networks. In this paper, we explore several drugs either in the clinic or under development for AD therapy in term of their design strategies, diverse mechanisms of action and disease-modifying potential. These drugs act as multi-target ligands and may serve as leads for further development as network medicines. View Full-Text
Keywords: memantine; nitromemantine; NMDA antagonist; M30; M30D; AChE-MAO-A/B inhibitor; chelator; Ginkgo biloba memantine; nitromemantine; NMDA antagonist; M30; M30D; AChE-MAO-A/B inhibitor; chelator; Ginkgo biloba
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Zheng, H.; Fridkin, M.; Youdim, M. From Single Target to Multitarget/Network Therapeutics in Alzheimer’s Therapy. Pharmaceuticals 2014, 7, 113-135.

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