Anle138b | CAS# 882697-00-9 | oligomeric aggregate formation inhibitor

MedKoo Cat#: 563797 | Name: Anle138b

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Anle138b is an alpha-synuclein oligomerization inhibitor and novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson's disease.. Anle138b blocks the activity of conducting Aβ pores without changing the membrane embedded Aβ-oligomer structure, at the mechanistic level. Anle138b blocks interpeptide main chain interactions and impedes the spontaneous formation of ordered β-sheet structures, in particular those with out-of-register antiparallel β-strands.

Chemical Structure

Anle138b

CAS#882697-00-9

Theoretical Analysis

MedKoo Cat#: 563797

Name: Anle138b

CAS#: 882697-00-9

Chemical Formula: C16H11BrN2O2

Exact Mass: 342.0004

Molecular Weight: 343.18

Elemental Analysis: C, 56.00; H, 3.23; Br, 23.28; N, 8.16; O, 9.32

Price and Availability

Size	Price	Availability
10mg	USD 110.00	Ready to ship
25mg	USD 220.00	Ready to ship
50mg	USD 365.00	Ready to ship
100mg	USD 585.00	Ready to ship
200mg	USD 950.00	Ready to ship
500mg	USD 1,950.00	Ready to ship
1g	USD 3,250.00	Ready to ship
2g	USD 5,450.00	Ready to ship

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Related CAS #

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Synonym

Anle138b; Anle 138b; Anle-138b; Emrusolmin

IUPAC/Chemical Name

5-(1,3-Benzodioxol-5-yl)-3-(3-bromophenyl)-1H-pyrazole

InChi Key

RCQIIBJSUWYYFU-UHFFFAOYSA-N

InChi Code

InChI=1S/C16H11BrN2O2/c17-12-3-1-2-10(6-12)13-8-14(19-18-13)11-4-5-15-16(7-11)21-9-20-15/h1-8H,9H2,(H,18,19)

SMILES Code

BrC1=CC(C2=NNC(C3=CC=C(OCO4)C4=C3)=C2)=CC=C1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.03.00

More Info

Oral application of the compound anle138b restores hippocampal synaptic and transcriptional plasticity as well as spatial memory in a mouse model for Alzheimer's disease, when given orally before or after the onset of pathology.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot# A22T03K29

QC Data

View QC data: current batch, Lot# A22T03K29

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Anle138b, an oligomeric aggregation inhibitor, blocks the formation of pathological aggregates of prion protein (PrPSc) and of α-synuclein (α-syn).

In vitro activity:

To determine the effect of increasing doses of anle138b on melanoma cell viability and whether it is cytotoxic to the cells and thus compromises their plasma membrane integrity, this study performed a lactate dehydrogenase (LDH) cytotoxicity assay of culture supernatants collected from WM983-B and WM852 melanoma cells that were treated for 96 h with increasing doses of anle138b with replenishment of an equivalent dose of the compound at 48 h. The high-level α-synuclein–expressing WM983-B cells showed strong killing that reached a maximum at a 10 μM dose of anle138b, possibly due to its low solubility above this dose in serum-free medium. In comparison, the number of cells killed in response to anle138b treatment was significantly lower in the case of the low-level α-synuclein–expressing WM852 cells. Reference: Proc Natl Acad Sci U S A. 2017 Jun 20; 114(25): E4971–E4977.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5488931/

In vivo activity:

CP13 immunohistochemical staining revealed a clear visual reduction of tau deposition in hTau mice receiving Anle138b treatment when compared to the hTau vehicle group. Immunohistochemical quantitation indicated a 53% reduction of tau burden after 3 months of Anle138b treatment in the frontal cortex, relative to the burden in hTau vehicle mice (6.1% vs. 13%; p < 0.001). Similarly, there was 59% less tau burden in the hippocampus of the treated mice (1.9% vs 4.7; p < 0.001). There were fewer CP13-positive neurons in the Anle138b treatment group in the frontal cortex (− 33%; p < 0.001) and the hippocampus (− 14%; p < 0.001) when compared to the hTau vehicle group. Reference: Alzheimers Res Ther. 2019; 11: 67. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6670231/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	87.42
	DMSO	41.5	121.04

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 343.18 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Turriani E, Lázaro DF, Ryazanov S, Leonov A, Giese A, Schön M, Schön MP, Griesinger C, Outeiro TF, Arndt-Jovin DJ, Becker D. Treatment with diphenyl-pyrazole compound anle138b/c reveals that α-synuclein protects melanoma cells from autophagic cell death. Proc Natl Acad Sci U S A. 2017 Jun 20;114(25):E4971-E4977. doi: 10.1073/pnas.1700200114. Epub 2017 Jun 5. PMID: 28584093; PMCID: PMC5488931. 2. Wagner J, Ryazanov S, Leonov A, Levin J, Shi S, Schmidt F, Prix C, Pan-Montojo F, Bertsch U, Mitteregger-Kretzschmar G, Geissen M, Eiden M, Leidel F, Hirschberger T, Deeg AA, Krauth JJ, Zinth W, Tavan P, Pilger J, Zweckstetter M, Frank T, Bähr M, Weishaupt JH, Uhr M, Urlaub H, Teichmann U, Samwer M, Bötzel K, Groschup M, Kretzschmar H, Griesinger C, Giese A. Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson's disease. Acta Neuropathol. 2013 Jun;125(6):795-813. doi: 10.1007/s00401-013-1114-9. Epub 2013 Apr 19. PMID: 23604588; PMCID: PMC3661926. 3. Brendel M, Deussing M, Blume T, Kaiser L, Probst F, Overhoff F, Peters F, von Ungern-Sternberg B, Ryazanov S, Leonov A, Griesinger C, Zwergal A, Levin J, Bartenstein P, Yakushev I, Cumming P, Boening G, Ziegler S, Herms J, Giese A, Rominger A. Late-stage Anle138b treatment ameliorates tau pathology and metabolic decline in a mouse model of human Alzheimer's disease tau. Alzheimers Res Ther. 2019 Aug 1;11(1):67. doi: 10.1186/s13195-019-0522-z. PMID: 31370885; PMCID: PMC6670231. 4. Heras-Garvin A, Weckbecker D, Ryazanov S, Leonov A, Griesinger C, Giese A, Wenning GK, Stefanova N. Anle138b modulates α-synuclein oligomerization and prevents motor decline and neurodegeneration in a mouse model of multiple system atrophy. Mov Disord. 2019 Feb;34(2):255-263. doi: 10.1002/mds.27562. Epub 2018 Nov 19. PMID: 30452793; PMCID: PMC6492169.

In vitro protocol:

In vivo protocol:

1. Brendel M, Deussing M, Blume T, Kaiser L, Probst F, Overhoff F, Peters F, von Ungern-Sternberg B, Ryazanov S, Leonov A, Griesinger C, Zwergal A, Levin J, Bartenstein P, Yakushev I, Cumming P, Boening G, Ziegler S, Herms J, Giese A, Rominger A. Late-stage Anle138b treatment ameliorates tau pathology and metabolic decline in a mouse model of human Alzheimer's disease tau. Alzheimers Res Ther. 2019 Aug 1;11(1):67. doi: 10.1186/s13195-019-0522-z. PMID: 31370885; PMCID: PMC6670231. 2. Heras-Garvin A, Weckbecker D, Ryazanov S, Leonov A, Griesinger C, Giese A, Wenning GK, Stefanova N. Anle138b modulates α-synuclein oligomerization and prevents motor decline and neurodegeneration in a mouse model of multiple system atrophy. Mov Disord. 2019 Feb;34(2):255-263. doi: 10.1002/mds.27562. Epub 2018 Nov 19. PMID: 30452793; PMCID: PMC6492169.

1: Beauchemin KS, Rees JR, Supattapone S. Alternating anti-prion regimens reduce combination drug resistance but do not further extend survival in scrapie- infected mice. J Gen Virol. 2021 Dec;102(12):001705. doi: 10.1099/jgv.0.001705. PMID: 34904943; PMCID: PMC8744272. 2: Galkin M, Priss A, Topcheva O, Yushchenko DA, Shvadchak VV. FRET-based assay for intracellular evaluation of α-synuclein aggregation inhibitors. J Neurochem. 2021 Dec;159(5):901-912. doi: 10.1111/jnc.15528. Epub 2021 Nov 8. PMID: 34687236. 3: Pena-DIaz S, Ventura S. One ring is sufficient to inhibit α-synuclein aggregation. Neural Regen Res. 2022 Mar;17(3):508-511. doi: 10.4103/1673-5374.320973. PMID: 34380879; PMCID: PMC8504378. 4: Kuebler L, Buss S, Leonov A, Ryazanov S, Schmidt F, Maurer A, Weckbecker D, Landau AM, Lillethorup TP, Bleher D, Saw RS, Pichler BJ, Griesinger C, Giese A, Herfert K. [11C]MODAG-001-towards a PET tracer targeting α-synuclein aggregates. Eur J Nucl Med Mol Imaging. 2021 Jun;48(6):1759-1772. doi: 10.1007/s00259-020-05133-x. Epub 2020 Dec 28. PMID: 33369690; PMCID: PMC8113290. 5: Lemos M, Venezia S, Refolo V, Heras-Garvin A, Schmidhuber S, Giese A, Leonov A, Ryazanov S, Griesinger C, Galabova G, Staffler G, Wenning GK, Stefanova N. Targeting α-synuclein by PD03 AFFITOPE® and Anle138b rescues neurodegenerative pathology in a model of multiple system atrophy: clinical relevance. Transl Neurodegener. 2020 Sep 24;9(1):38. doi: 10.1186/s40035-020-00217-y. PMID: 32972456; PMCID: PMC7513530. 6: Dominguez-Meijide A, Vasili E, König A, Cima-Omori MS, Ibáñez de Opakua A, Leonov A, Ryazanov S, Zweckstetter M, Griesinger C, Outeiro TF. Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization. Sci Rep. 2020 Jul 30;10(1):12827. doi: 10.1038/s41598-020-69744-y. PMID: 32732936; PMCID: PMC7393090. 7: Ryan P, Xu M, Jahan K, Davey AK, Bharatam PV, Anoopkumar-Dukie S, Kassiou M, Mellick GD, Rudrawar S. Novel Furan-2-yl-1H-pyrazoles Possess Inhibitory Activity against α-Synuclein Aggregation. ACS Chem Neurosci. 2020 Aug 5;11(15):2303-2315. doi: 10.1021/acschemneuro.0c00252. Epub 2020 Jul 8. PMID: 32551538. 8: Burke CM, Mark KMK, Kun J, Beauchemin KS, Supattapone S. Emergence of prions selectively resistant to combination drug therapy. PLoS Pathog. 2020 May 18;16(5):e1008581. doi: 10.1371/journal.ppat.1008581. PMID: 32421750; PMCID: PMC7259791. 9: Brendel M, Deussing M, Blume T, Kaiser L, Probst F, Overhoff F, Peters F, von Ungern-Sternberg B, Ryazanov S, Leonov A, Griesinger C, Zwergal A, Levin J, Bartenstein P, Yakushev I, Cumming P, Boening G, Ziegler S, Herms J, Giese A, Rominger A. Late-stage Anle138b treatment ameliorates tau pathology and metabolic decline in a mouse model of human Alzheimer's disease tau. Alzheimers Res Ther. 2019 Aug 1;11(1):67. doi: 10.1186/s13195-019-0522-z. PMID: 31370885; PMCID: PMC6670231. 10: Wegrzynowicz M, Bar-On D, Calo' L, Anichtchik O, Iovino M, Xia J, Ryazanov S, Leonov A, Giese A, Dalley JW, Griesinger C, Ashery U, Spillantini MG. Depopulation of dense α-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson's disease model. Acta Neuropathol. 2019 Oct;138(4):575-595. doi: 10.1007/s00401-019-02023-x. Epub 2019 May 31. PMID: 31165254; PMCID: PMC6778064. 11: Qin K, Zhao L, Solanki A, Busch C, Mastrianni J. Anle138b prevents PrP plaque accumulation in Tg(PrP-A116V) mice but does not mitigate clinical disease. J Gen Virol. 2019 Jun;100(6):1027-1037. doi: 10.1099/jgv.0.001262. Epub 2019 May 2. PMID: 31045489. 12: Heras-Garvin A, Weckbecker D, Ryazanov S, Leonov A, Griesinger C, Giese A, Wenning GK, Stefanova N. Anle138b modulates α-synuclein oligomerization and prevents motor decline and neurodegeneration in a mouse model of multiple system atrophy. Mov Disord. 2019 Feb;34(2):255-263. doi: 10.1002/mds.27562. Epub 2018 Nov 19. PMID: 30452793; PMCID: PMC6492169. 13: Reiner AM, Schmidt F, Ryazanov S, Leonov A, Weckbecker D, Deeg AA, Griesinger C, Giese A, Zinth W. Photophysics of diphenyl-pyrazole compounds in solutions and α-synuclein aggregates. Biochim Biophys Acta Gen Subj. 2018 Apr;1862(4):800-807. doi: 10.1016/j.bbagen.2017.12.007. Epub 2017 Dec 19. PMID: 29273222. 14: Martinez Hernandez A, Urbanke H, Gillman AL, Lee J, Ryazanov S, Agbemenyah HY, Benito E, Jain G, Kaurani L, Grigorian G, Leonov A, Rezaei-Ghaleh N, Wilken P, Arce FT, Wagner J, Fuhrmann M, Caruana M, Camilleri A, Vassallo N, Zweckstetter M, Benz R, Giese A, Schneider A, Korte M, Lal R, Griesinger C, Eichele G, Fischer A. The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology. EMBO Mol Med. 2018 Jan;10(1):32-47. doi: 10.15252/emmm.201707825. PMID: 29208638; PMCID: PMC5760857. 15: Guix FX, Dotti CG. Could blocking the formation of amyloid channels rescue Alzheimer's phenotype? EMBO Mol Med. 2018 Jan;10(1):7-9. doi: 10.15252/emmm.201708491. PMID: 29208637; PMCID: PMC5760883. 16: Matthes D, Gapsys V, Griesinger C, de Groot BL. Resolving the Atomistic Modes of Anle138b Inhibitory Action on Peptide Oligomer Formation. ACS Chem Neurosci. 2017 Dec 20;8(12):2791-2808. doi: 10.1021/acschemneuro.7b00325. Epub 2017 Sep 28. PMID: 28906103. 17: Turriani E, Lázaro DF, Ryazanov S, Leonov A, Giese A, Schön M, Schön MP, Griesinger C, Outeiro TF, Arndt-Jovin DJ, Becker D. Treatment with diphenyl- pyrazole compound anle138b/c reveals that α-synuclein protects melanoma cells from autophagic cell death. Proc Natl Acad Sci U S A. 2017 Jun 20;114(25):E4971-E4977. doi: 10.1073/pnas.1700200114. Epub 2017 Jun 5. PMID: 28584093; PMCID: PMC5488931. 18: Teruya K, Doh-Ura K. Insights from Therapeutic Studies for PrP Prion Disease. Cold Spring Harb Perspect Med. 2017 Mar 1;7(3):a024430. doi: 10.1101/cshperspect.a024430. PMID: 27836910; PMCID: PMC5334251. 19: Fellner L, Kuzdas-Wood D, Levin J, Ryazanov S, Leonov A, Griesinger C, Giese A, Wenning GK, Stefanova N. Anle138b Partly Ameliorates Motor Deficits Despite Failure of Neuroprotection in a Model of Advanced Multiple System Atrophy. Front Neurosci. 2016 Mar 10;10:99. doi: 10.3389/fnins.2016.00099. PMID: 27013960; PMCID: PMC4785146. 20: Wagner J, Krauss S, Shi S, Ryazanov S, Steffen J, Miklitz C, Leonov A, Kleinknecht A, Göricke B, Weishaupt JH, Weckbecker D, Reiner AM, Zinth W, Levin J, Ehninger D, Remy S, Kretzschmar HA, Griesinger C, Giese A, Fuhrmann M. Reducing tau aggregates with anle138b delays disease progression in a mouse model of tauopathies. Acta Neuropathol. 2015 Nov;130(5):619-31. doi: 10.1007/s00401-015-1483-3. Epub 2015 Oct 6. PMID: 26439832; PMCID: PMC4612332.