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KDS2010, a Newly Developed Reversible MAO-B Inhibitor, as an Effective Therapeutic Candidate for Parkinson’s Disease

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Title
KDS2010, a Newly Developed Reversible MAO-B Inhibitor, as an Effective Therapeutic Candidate for Parkinson’s Disease
Author(s)
Nam, Min-Ho; Park, Jong-Hyun; Song, Hyo Jung; Choi, Ji Won; Kim, Siwon; Jang, Bo Ko; Yoon, Hyung Ho; Heo, Jun Young; Lee, Hyowon; Heeyoung An; Kim, Hyeon Jeong; Park, Sun Jun; Cho, Doo-Wan; Yang, Young-Su; Han, Su-Cheol; Kim, Sangwook; Oh, Soo-Jin; Jeon, Sang Ryong; Park, Ki Duk; C. Justin Lee
Publication Date
2021-10
Journal
Neurotherapeutics, v.18, no.3, pp.1729 - 1747
Publisher
Springer Science and Business Media Deutschland GmbH
Abstract
© 2021, The Author(s).Monoamine oxidase-B (MAO-B) is a well-established therapeutic target for Parkinson’s disease (PD); however, previous clinical studies on currently available irreversible MAO-B inhibitors have yielded disappointing neuroprotective effects. Here, we tested the therapeutic potential of KDS2010, a recently synthesized potent, selective, and reversible MAO-B inhibitor in multiple animal models of PD. We designed and synthesized a series of α-aminoamide derivatives and found that derivative KDS2010 exhibited the highest potency, specificity, reversibility, and bioavailability (> 100%). In addition, KDS2010 demonstrated significant neuroprotective and anti-neuroinflammatory efficacy against nigrostriatal pathway destruction in the mouse MPTP model of parkinsonism. Treatment with KDS2010 also alleviated parkinsonian motor dysfunction in 6-hydroxydopamine-induced and A53T mutant α-synuclein overexpression rat models of PD. Moreover, KDS2010 showed virtually no toxicity or side effects in non-human primates. KDS2010 could be a next-generation therapeutic candidate for PD.
URI
https://pr.ibs.re.kr/handle/8788114/10834
DOI
10.1007/s13311-021-01097-4
ISSN
1933-7213
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > 1. Journal Papers (저널논문)
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