Anle138b
(Synonyms: 3-(1,3-苯并二恶唑-5-基)-5-(3-溴苯基)-1H-吡唑) 目录号 : GC30846
Anle138b是一种毒性低，口服生物利用度高并能穿透血脑屏障的低聚物聚集抑制剂，能够阻止朊蛋白（PrPSc）和α-突触核蛋白（α-syn）的病理性聚集物的形成。
Cas No.:882697-00-9
Sample solution is provided at 25 µL, 10mM.
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Anle138b is a low polymer aggregation inhibitor with low toxicity, high oral bioavailability, and the ability to penetrate the blood-brain barrier. It can prevent the formation of pathological aggregates of prion protein (PrPSc) and α-synuclein [1]. Protein aggregates (also known as prion-like transmission) transfer between cells in the brain, leading to neurodegenerative diseases. Polymer aggregates are considered key neurotoxins [2]. Anle138b can be used in the research of neurodegenerative diseases (such as prion diseases, Parkinson's disease, etc.) [3-4].
In vitro, Anle138b (7μM; 16h) treatment reduced the formation of mHTT aggregates in human neural precursor cells (NPCs) and improved neurotoxicity [5]. Anle138b (10 and 30mM; 48h) treatment significantly changed the cell morphology of human melanoma cell lines and inhibited their proliferation, disrupted their plasma membranes and mitochondrial membrane potential, and led to autophagy dysregulation [6].
In vivo, Anle138b (2g/kg for 7 days diet) significantly changed the morphology of tumor tissues in WM983-B (MGP) human melanoma xenograft mice through oral treatment, and increased the number of LC3-positive cells [6]. Anle138b (0.6and 2 g/kg for 4-month diet) significantly reduced the α-synuclein oligomers and neuroglial cytoplasmic inclusions in PLP-hαSyn mice and protected dopaminergic neurons from death and reduced the activation of microglia in the substantia nigra [7].
References:
[1] Wagner J, Ryazanov S, Leonov A, et al. Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson’s disease[J]. Acta neuropathologica, 2013, 125(6): 795-813.
[2] Sidoryk-Węgrzynowicz M, Adamiak K, Strużyńska L. Targeting protein misfolding and aggregation as a therapeutic perspective in neurodegenerative disorders[J]. International Journal of Molecular Sciences, 2024, 25(22): 12448.
[3] Martinez Hernandez A, et al. The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology. EMBO Mol Med. 2018;10(1):32-47.
[4] Levin J, Sing N, Melbourne S, et al. Safety, tolerability and pharmacokinetics of the oligomer modulator anle138b with exposure levels sufficient for therapeutic efficacy in a murine Parkinson model: A randomised, double-blind, placebo-controlled phase 1a trial[J]. EBioMedicine, 2022, 80.
[5] da Silva Padilha M, Koyuncu S, Chabanis E, et al. Anle138b ameliorates pathological phenotypes in mouse and cellular models of Huntington’s disease[J]. bioRxiv, 2025: 2025.03. 11.642540.
[6] Turriani E, Lázaro D F, Ryazanov S, et al. Treatment with diphenyl–pyrazole compound anle138b/c reveals that α-synuclein protects melanoma cells from autophagic cell death[J]. Proceedings of the National Academy of Sciences, 2017, 114(25): E4971-E4977.
[7] Heras-Garvin A, Weckbecker D, Ryazanov S, et al. Anle138b modulates α-synuclein oligomerization and prevents motor decline and neurodegeneration in a mouse model of multiple system atrophy. Mov Disord. 2019;34(2):255-263.
Anle138b是一种毒性低，口服生物利用度高并能穿透血脑屏障的低聚物聚集抑制剂，能够阻止朊蛋白（PrPSc）和α-突触核蛋白（α-syn）的病理性聚集物的形成 [1]。蛋白质聚集物（也被称为朊病毒样传播）会在脑内细胞之间进行转移，从而导致神经退行性病变。低聚物聚集体被认为是关键的神经毒剂 [2]。Anle138b可用于神经退行性疾病（如朊病毒、帕金森氏病等）的治疗研究 [3-4]。
在体外，Anle138b（7μM; 16h）处理减少了人类神经前体细胞（NPCs）中mHTT聚集体的形成并改善了神经毒性 [5]。Anle138b（10 and 30mM; 48h）处理显著改变了人黑色素瘤细胞系的细胞形态并抑制其增殖，破坏其质膜和线粒体膜电位，并且导致自噬失调 [6]。
在体内，Anle138b（2g/kg for 7 days diet）通过口服治疗显著改变了WM983-B（MGP）人黑色素瘤异种移植小鼠中肿瘤组织的形态，并增加了LC3阳性细胞的数量 [6]。Anle138b（0.6 and 2g/kg for 4 months diet）通过口服治疗显著减少了PLP-hαSyn小鼠体内的α-突触核蛋白寡聚体和神经胶质细胞质包裹体，保护多巴胺能神经元存活并减少黑质中小胶质细胞的活化 [7]。
| Kinase experiment [1]: | |
Preparation Method | Kinase experiments were performed in 50mM Tris-buffer (pH 7.0) in a total volume of 20μl in 384- or 96-well plates with a cover slide bottom. The concentration of α-syn was approximately 20nM. Anle138b were diluted into the assay mixture from 10-fold stock solutions containing 10% DMSO (v/v), resulting in a final concentration of 1% DMSO in all samples. Experiments were started by diluting the 5-fold stock solution of fluorescently labelled α-syn in 50mM Tris-buffer, pH 7.0, containing 1% DMSO, 10μM FeCl3 and Anle138b in concentrations ranging from 1–10μM. Aggregation was monitored at room temperature for at least 2.5h in 3–4 independent samples for each experimental group. |
Reaction Conditions | 1–10μM; 2.5h |
Applications | Anle138b inhibits the formation of α-syn oligomers in a dose-dependent manner, with an EC50 value of 2.8μM. |
| Cell experiment [2]: | |
Cell lines | Melanoma cells |
Preparation Method | 10 or 30mM stock solutions of Anle138b were made in DMSO. Melanoma cells were plated for 24h in tissue-culture medium containing 10% FBS and rinsed three times with serum-free medium before addition of Anle138b, anle138c, or an equivalent volume of DMSO only in serum-free medium. Forty-eight hours later, the cell culture medium was removed, followed by addition of an equivalent dose of Anle138b or DMSO only in serum-free culture medium. 20ng/mL of recombinant human basic fibroblast growth factor was added to the serum-free culture medium during treatment of these cells with Anle138b. Proliferation of melanoma cells that had received DMSO only or were treated with Anle138b was determined by counting the cells with a hemocytometer. |
Reaction Conditions | 10 and 30mM; 48h |
Applications | Anle138b significantly altered the cell morphology of human melanoma cell lines and inhibited their proliferation. |
| Animal experiment [3]: | |
Animal models | C57/BL6 mice (PLP‐hαSyn mice overexpressing wild‐type human α‐syn) |
Preparation Method | Two‐month‐old male transgenic mice were randomized in three different groups: one fed with placebo food pellets (n = 10), another fed with pellets containing Anle138b at 0.6g/kg of food (n = 8), and a last group fed with pellets containing 2g of Anle138b per kg of food (n = 10). The dose of 2g of Anle138b per kg of food was used in previous experiments in mice and establishes during the wake phase a concentration of 60μM in the brain. Two‐month‐old C57/BL6 healthy nontransgenic animals (WT) fed with placebo pellets were used as a healthy control (n = 10). Food pellets were provided to the animals throughout the whole experiment. After 4 months of treatment, behavioral analysis was conducted. Subsequently, the animals were euthanized and their brains were extracted for immunohistochemical analysis. |
Dosage form | 0.6 and 2 g/kg for 4 months; oral |
Applications | Anle138b significantly reduced the α-synuclein oligomers and neuroglial cytoplasmic inclusions in mice, and also decreased the activation of microglia in the substantia nigra. |
References: | |
| Cas No. | 882697-00-9 | SDF | |
| 别名 | 3-(1,3-苯并二恶唑-5-基)-5-(3-溴苯基)-1H-吡唑 | ||
| Canonical SMILES | BrC1=CC(C2=CC(C3=CC=C(OCO4)C4=C3)=NN2)=CC=C1 | ||
| 分子式 | C16H11BrN2O2 | 分子量 | 343.17 |
| 溶解度 | DMSO : ≥ 50 mg/mL (145.70 mM);Water : < 0.1 mg/mL (insoluble) | 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.914 mL | 14.57 mL | 29.1401 mL |
| 5 mM | 582.8 μL | 2.914 mL | 5.828 mL |
| 10 mM | 291.4 μL | 1.457 mL | 2.914 mL |
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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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2.
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Quality Control & SDS
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- Purity: >98.00%
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