biostudies-literatureDas BNIH/NINDSNational Institute of Neurological Disorders and Stroke/National Institute of HealthWayne State President Research EnhancementNINDS NIH HHS88-99https://www.ebi.ac.uk/biostudies/studies/S-EPMC5542047biostudies-literatureUnknown123Here, we report the characterization of a novel hybrid D₂/D₃ agonist and iron (II) specific chelator, D-607, as a multi-target-directed ligand against Parkinson's disease (PD). In our previously published report, we showed that D-607 is a potent agonist of dopamine (DA) D₂/D₃ receptors, exhibits efficacy in a reserpinized PD animal model and preferentially chelates to iron (II). As further evidence of its potential as a neuroprotective agent in PD, the present study reveals D-607 to be protective in neuronal PC12 cells against 6-OHDA toxicity. In an in vivo Drosophila melanogaster model expressing a disease-causing variant of α-synuclein (α-Syn) protein in fly eyes, the compound was found to significantly suppress toxicity compared to controls, cNeuropharmacologyA novel iron (II) preferring dopamine agonist chelator D-607 significantly suppresses α-syn- and MPTP-induced toxicities in vivo.PMC5542047R01 NS086778NS047198NS086778R01 NS047198Xu LDutta AKDas BRajagopalan STodi SVJoshi GSAndersen JKLuo DfalseA novel iron (II) preferring dopamine agonist chelator D-607 significantly suppresses α-syn- and MPTP-induced toxicities in vivo.Here, we report the characterization of a novel hybrid D₂/D₃ agonist and iron (II) specific chelator, D-607, as a multi-target-directed ligand against Parkinson's disease (PD). In our previously published report, we showed that D-607 is a potent agonist of dopamine (DA) D₂/D₃ receptors, exhibits efficacy in a reserpinized PD animal model and preferentially chelates to iron (II). As further evidence of its potential as a neuroprotective agent in PD, the present study reveals D-607 to be protective in neuronal PC12 cells against 6-OHDA toxicity. In an in vivo Drosophila melanogaster model expressing a disease-causing variant of α-synuclein (α-Syn) protein in fly eyes, the compound was found to significantly suppress toxicity compared to controls, c2017-01-01T00:00:00Z2017 Sep2025-04-04T00:47:09.108Z2019-03-26T23:53:00ZS-EPMC55420472853316410.1016/j.neuropharm.2017.05.019