GPI-1485
(Synonyms: 1-(1,2-二氧代-3,3-二甲基戊基)-2(S)-2吡咯烷甲酸,GM1485) 目录号 : GC39809
GPI-1485是一种非免疫抑制性的FKBP52特异性配体。
Cas No.:186268-78-0
Sample solution is provided at 25 µL, 10mM.
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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]。
| Cell experiment [1]: | |
Cell lines | Normal human dermal fibroblasts |
Preparation Method | Normal human dermal fibroblasts (NHDF) were seeded onto poly-D-lysine-coated coverslips at a density of 4,000cells/well in a 24-well plate, and cultured overnight in PromoCell’s NHDF growth medium. The medium was aspirated, wells were rinsed twice with Hank’s balanced salt solution, and 400μl of serum-free medium with either 100μM GPI-1485 dissolved in DMEM or an equal volume of DMEM alone was added. The cells were cultured for 3 days, fixed, and stained for expression of Oct4/Sox2, and RNA was harvested for gene expression studies. Parallel cultures were treated identically, and, after 3 days of culture, the media were switched to conditions shown to drive embryonic stem cells down a neural lineage, and the cells were stained for neural-specific antigens. |
Reaction Conditions | 100μM; 3 days |
Applications | GPI-1485 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. |
| Animal experiment [1]: | |
Animal models | Adult male Wistar rats |
Preparation Method | Adult male Wistar rats, weighing 250-300g, were housed in standard cages with free access to food and water on a 12-hr light/dark cycle. Animals were anesthetized with isoflurane in a mixture of 70% nitrous oxide/30% oxygen and positioned supine under a temperature-controlled heat lamp. Core temperature was maintained at 37℃ throughout the entire procedure and for 60min postreperfusion. The right common carotid artery and internal carotid artery were exposed. MCA occlusion was accomplished by advancing a 25mm suture of diameter 4-0 with a blunted silicone tip (outer diameter 0.38mm) through an incision in the external carotid artery until the suture was 18mm past the bifurcation. MCA occlusion was confirmed by transcranial measurements of cerebral blood flow (CBF) by laser Doppler flowmetry. Animals were included only if CBF was reduced to <40% of baseline; animals that did not exhibit this criterion were prospectively excluded. After 120min of ischemia, the occluding suture was removed, and reperfusion was confirmed. Beginning 24h post-ischemia, animals received daily, intraperitoneal injections of GPI-1485 (5mg/kg/day) or vehicle, for a total of 42 days. Additionally, on days 1–14, animals received intraperitoneal injections of BrdU (50mg/kg). Animals were sacrificed for histologic analysis following neurological evaluation on day 42. Eighteen animals were randomized to each cohort. |
Dosage form | 5mg/kg/day; intraperitoneal injections for 42 days beginning 24h post-ischemia |
Applications | GPI-1485 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. |
References: | |
| Cas No. | 186268-78-0 | SDF | |
| 别名 | 1-(1,2-二氧代-3,3-二甲基戊基)-2(S)-2吡咯烷甲酸,GM1485 | ||
| Canonical SMILES | O=C(O)[C@H]1N(C(C(C(C)(C)CC)=O)=O)CCC1 | ||
| 分子式 | C12H19NO4 | 分子量 | 241.28 |
| 溶解度 | DMSO : 100 mg/mL (414.46 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.1446 mL | 20.7228 mL | 41.4456 mL |
| 5 mM | 828.9 μL | 4.1446 mL | 8.2891 mL |
| 10 mM | 414.5 μL | 2.0723 mL | 4.1446 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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Quality Control & SDS
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- Purity: >98.00%
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