GPI-1485 is a non-immunosuppressive FKBP52-specific ligand[1]. FKBP52 (FK506-binding protein 52) is a peptidyl-prolyl isomerase and molecular chaperone, a key regulatory subunit of steroid hormone receptor complexes involved in neuroprotection, stress response, and hormone signal transduction[2][3]. GPI-1485 selectively binds to FKBP52 and retains neuroprotective activity without immunosuppressive side effects[4]. GPI-1485 is commonly used in research on neurofunctional impairment and regeneration in neurodegenerative diseases such as Parkinson's disease[5][6].
In vitro, GPI-1485 (100μM; 3 days) reprogrammed human dermal fibroblasts under oxidative stress to a stem-cell-like phenotype expressing Oct4, Sox2, nanog, and lin28, and these cells subsequently differentiated into neuronal (βIII-tubulin, NSE-positive) and glial (GFAP, S100β-positive) lineages when cultured in neural-inducing conditions[7].
In vivo, GPI-1485 (5mg/kg/day; intraperitoneal injections for 42 days beginning 24h post-ischemia) improved neurological function scores and increased Sox2-positive neural precursor cells in the ipsilateral subventricular zone and striatum of rats with transient middle cerebral artery occlusion[7].
References:
[1] Marshall VL, Grosset DG. GPI-1485 (Guilford). Curr Opin Investig Drugs. 2004;5(1):107-112.
[2] Davies TH, Sánchez ER. FKBP52. Int J Biochem Cell Biol. 2005;37(1):42-47.
[3] Chambraud B, Byrne C, Meduri G, Baulieu EE, Giustiniani J. FKBP52 in Neuronal Signaling and Neurodegenerative Diseases: A Microtubule Story. Int J Mol Sci. 2022;23(3):1738.
[4] Poulter MO, Payne KB, Steiner JP. Neuroimmunophilins: a novel drug therapy for the reversal of neurodegenerative disease?. Neuroscience. 2004;128(1):1-6.
[5] NINDS NET-PD Investigators. A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease. Neurology. 2007;68(1):20-28.
[6] Parashos SA, Luo S, Biglan KM, et al. Measuring disease progression in early Parkinson disease: the National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) experience. JAMA Neurol. 2014;71(6):710-716.
[7] Ducruet AF, DeRosa PA, Zacharia BE, Sosunov SA, Connolly ES Jr, Weinstein DE. GM1485, a nonimmunosuppressive immunophilin ligand, promotes neurofunctional improvement and neural regeneration following stroke. J Neurosci Res. 2012;90(7):1413-1423.
GPI-1485是一种非免疫抑制性的FKBP52特异性配体[1]。FKBP52（FK506结合蛋白52）是一种肽基脯氨酰异构酶和分子伴侣，是类固醇激素受体复合物的关键调节亚基，参与神经保护、应激反应和激素信号转导[2][3]。GPI-1485选择性结合FKBP52，保留神经保护活性而无免疫抑制副作用[4]。GPI-1485常用于神经退行性疾病（如帕金森病）的神经功能损伤与再生研究[5][6]。
在体外，GPI-1485（100μM；3天）将氧化应激条件下的人真皮成纤维细胞重编程为表达Oct4、Sox2、nanog和lin28的干细胞样表型，这些细胞随后在神经诱导条件下分化为神经元（βIII-tubulin、NSE阳性）和胶质细胞（GFAP、S100β阳性）谱系[7]。
在体内，GPI-1485（5mg/kg/天；腹腔注射；缺血后24小时开始；共42天）改善了大鼠短暂性大脑中动脉闭塞模型的神经功能评分，并增加了同侧脑室下区和纹状体中的Sox2阳性神经前体细胞[7]。