KDS2010, a Newly Developed Reversible MAO-B Inhibitor,as an Effective Therapeutic Candidate for Parkinson’s Disease |
| |
Authors: | Min-Ho Nam Jong-Hyun Park Hyo Jung Song Ji Won Choi Siwon Kim Bo Ko Jang Hyung Ho Yoon Jun Young Heo Hyowon Lee Heeyoung An Hyeon Jeong Kim Sun Jun Park Doo-Wan Cho Young-Su Yang Su-Cheol Han Sangwook Kim Soo-Jin Oh Sang Ryong Jeon Ki Duk Park C. Justin Lee |
| |
Abstract: | 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.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01097-4. |
| |
Keywords: | MAO-B inhibitor, Parkinson’ s disease, Pharmacology, α -Aminoamide derivative, Reactive glia |
|
|