GPI-1046

GPI-1046 is an orally active, antibiotic-free immunophilin ligand that reduces ethanol intake by upregulating glutamate transporter 1 (GLT1) in the prefrontal cortex (PFC) and nucleus accumbens core (NAc-core). GPI-1046 improves human immunodeficiency virus (HIV)-associated sensory neuropathy (HIV-SN) by attenuating store-operated calcium (SOC) entry. GPI-1046 has neuroprotective activity^[1][2][3]. IC50 & Target:GLT1^[1] In Vitro:GPI-1046 (1-1000 nM, 15 hours) protects neurites from damage in a dose-dependent manner in gp120-induced dorsal root ganglion (DRG) neurons^[2].
GPI-1046 (100 nM) protects gp120-induced DRG neurons from neurite damage by reducing IP3 receptor-mediated calcium release through lowering endoplasmic reticulum calcium and reducing calcium ion entry into cells by SOC^[2].
In Vivo:GPI-1046 (10-20 mg/kg, i.p., once a day for eight days) significantly reduces ethanol intake in an alcohol-preferring rat model without affecting body weight and sucrose intake^[1].
GPI-1046 (50 mg/kg, p.o., once a day, for 1-4 weeks) significantly raises the expression and function of GLT1 and has a neuroprotective effect^[3].
GPI-1046 (50 mg/kg, p.o., twice a day, until death) effectively prolongs the survival of mice with amyotrophic lateral sclerosis (ALS) and significantly increases the level of GLT1 protein^[3].