Nam, Min-Ho Park, Jong-Hyun Song, Hyo jung Choi, Ji Won Kim, Siwon 장보고 Yoon, Hyung Ho Heo, Jun Young Lee, Hyowon An, Heeyoung 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 Lee, C. Justin 2024-01-19T14:04:22Z 2024-01-19T14:04:22Z 2022-01-10 2021-07 1933-7213 https://pubs.kist.re.kr/handle/201004/116719 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 alpha-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 alpha-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. English SPRINGER KDS2010, a Newly Developed Reversible MAO-B Inhibitor, as an Effective Therapeutic Candidate for Parkinson's Disease Article 10.1007/s13311-021-01097-4 1 NEUROTHERAPEUTICS, v.18, no.3, pp.1729 - 1747 NEUROTHERAPEUTICS 18 3 1729 1747 N scie scopus 000703828900001 2-s2.0-85116492185 Clinical Neurology Neurosciences Pharmacology & Pharmacy Neurosciences & Neurology Pharmacology & Pharmacy Article MONOAMINE-OXIDASE B RAT MODEL MOUSE MODELS MPTP DERIVATIVES METABOLISM ASTROCYTES AGONISTS GABA MICE MAO-B inhibitor Parkinson&apos s disease Pharmacology alpha-Aminoamide derivative Reactive glia