Anle138b |
Katalog-Nr.GC30846
One-Click Copy Product Info
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Anle138b, ein oligomerer Aggregationsinhibitor, blockiert die Bildung pathologischer Aggregate von Prionprotein (PrPSc) und α-Synuclein (α-syn).
Products are for research use only. Not for human use. We do not sell to patients.
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.
| 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 | |
| Canonical SMILES | BrC1=CC(C2=CC(C3=CC=C(OCO4)C4=C3)=NN2)=CC=C1 | ||
| Formula | C16H11BrN2O2 | M.Wt | 343.17 |
| Löslichkeit | DMSO : ≥ 50 mg/mL (145.70 mM);Water : < 0.1 mg/mL (insoluble) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 5 reference(s) in Google Scholar.)