ML417

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

ML417 是 D3 多巴胺的选择性脑渗透激动剂 (EC50：38 nM)。分子模型表明 ML417 以独特的方式与 D3R 相互作用，这可能解释了其卓越的选择性。

ML417 is a selective and brain penetrant agonist of D3 Dopamine (EC50 : 38 nM).Molecular modeling suggests that ML417 interacts with the D3R in a unique manner, possibly explaining its remarkable selectivity.?ML417 was also found to protect against neurodegeneration of dopaminergic neurons derived from iPSCs.?Together with promising pharmacokinetics and toxicology profiles, these results suggest that ML417 is a novel and uniquely selective D3R agonist that may serve as both a research tool and a therapeutic lead for the treatment of neuropsychiatric disorders.

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.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.ML417 protects (0.005-5 μM; 24 hours) D3R-expressing dopaminergic neurons from 6-OHDA induced cell death.

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. Animal Model:6-8 week old male C57BL/6 mice 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.

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GPCR/G Protein

Dopamine Receptor

D3

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1386162-69-1

379.45

C22H25N3O3

>98% (HPLC)

DMSO:50 mg/mL (131.77 mM; Need ultrasonic)

COc1ccc(OCCN2CCN(CC2)C(=O)c2cc3ccccc3[nH]2)cc1

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(-20℃)

With Ice Pack

≥ 2 years