GPI-1046 是一种无抗生素作用的亲免素配体，部分通过上调 PFC 和 NAc 核心中的谷氨酸转运蛋白 1 来减少乙醇摄入。

GPI-1046 is an immunophilin ligand without antibiotic action and attenuates ethanol intake in part through the upregulation of glutamate transporter 1 (GLT1) in PFC and NAc-core.

GPI-1046 is an analog of FK506, which is an immunophilin ligand that has been shown neuroprotective effects in neurodegenerative disease models [1]. GPI-1046 readily crosses the blood-brain barrier and promotes the regeneration of dopamine (DA) cells in the CNS in association with functional recovery in rodent models [2]. GPI-1046 improves the HIV-associated injury of peripheral nerves [3].

Significant dose-dependent effects in the reduction of ethanol intake starting 48 h after the first treatment with GPI-1046 throughout treatment and post-treatment periods.?There were also dose-dependent increases in water intake.?However, GPI-1046 treatment did not affect the body weight of all animals nor sucrose intake.?Importantly, GPI-1046 (20mg/kg) increased GLT1 level compared to all groups in nucleus accumbens core (NAc-core).?Alternatively, GPI-1046 (10mg/kg) upregulated GLT1 level in NAc-core compared to vehicle (ethanol na?ve) group.?Moreover, both doses of GPI-1046 increased significantly GLT1 level in the prefrontal cortex (PFC) compared to ethanol na?ve vehicle group.?GPI-1046 (20mg/kg) increased GLT1 level in PFC compared to na?ve control group that was exposed to water and food only.?These findings demonstrated that neuroimmunophilin GPI-1046 attenuates ethanol intake in part through the upregulation of GLT1 in PFC and NAc-core[1].

186452-09-5

C20H28N2O4

360.45

1-(1,2-二氧代-3,3-二甲基戊基)-L脯氨酸-(3-吡啶基)-丙酯

DMSO:100 mg/mL (277.43 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years