| Description |
ML417 is a selective and brain penetrant D3 dopamine receptor (D3R) agonist, with an EC50 of 38 nM. ML417 potently promotes D3R-mediated β-arrestin translocation, G protein mediated signaling, and pERK phosphorylation with minimal effects on other GPCR-mediated signaling. ML417 exhibits neuroprotection against toxin-induced neurodegeneration of dopaminergic neurons[1].
|
| Related Catalog |
|
| Target |
D3 Receptor:38 nM (EC50)
|
| In Vitro |
ML417 exhibits a Ki for the D3R of 1.24 µM. ML417 is a full and potent agonist for multiple signaling pathways associated with D3R activation[1]. ML417 potently inhibits cAMP accumulation with an EC50 of 86 nM and an efficacy identical to that of dopamine. ML417 exhibits submicromolar affinity for only three of the targets, the β1-adrenergic, 5-HT2B serotoninergic, and σ-1 receptors. ML417 stimulates β-arrestin recruitment to the D3R-WT with an EC50 of 1.4 nM[1]. ML417 protects (0.005-5 μM; 24 hours) D3R-expressing dopaminergic neurons from 6-OHDA induced cell death[1].
|
| In Vivo |
In vivo pharmacokinetics experiments in mice (using 20 mg/kg; i.p.) reveals that ML417 is brain penetrant and exhibits a plasma half-life of 3.44 hours and a brain half-life of 4.23 hours. ML417 displays a plasma Tmax of 0.5 hours and Cmax of 6500 ng/ml, and a brain Tmax of 0.25 hours and Cmax of 28000 ng/ml[1]. Animal Model: 6-8 week old male C57BL/6 mice[1] Dosage: 20 mg/kg Administration: I.p. (Pharmacokinetic Analysis) Result: Brain penetrant and exhibits a plasma half-life of 3.44 hours and a brain half-life of 4.23 hours. Displayed a plasma Tmax of 0.5 hours and Cmax of 6500 ng/ml, and a brain Tmax of 0.25 hours and Cmax of 28000 ng/ml.
|
| References |
[1]. Moritz AE, et al. Discovery, Optimization, and Characterization of ML417: A Novel and Highly Selective D3 Dopamine Receptor Agonist. J Med Chem. 2020;63(10):5526‐5567.
|
