WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H208462
CAS#: 1232841-78-9 (HBr)
Description: ATH434, also known as PBT434, is a novel, brain-penetrant, inhibitor of α-synuclein aggregation. In transgenic animal models of Parkinson disease (A53T) and MSA (PLP-α-Syn), PBT434 reduced α-synuclein aggregation, preserved neurons and improved motor function. Glial cell inclusions were also reduced in a murine MSA model. PBT434 is thought to act by redistributing reactive iron across membranes, thereby blocking intracellular protein aggregation and oxidative stress. The affinity of PBT434 for iron is greater than that of α-synuclein but lower than that of iron trafficking proteins, e.g., ferritin.
Hodoodo Cat#: H208462
Name: ATH434 HBr
CAS#: 1232841-78-9 (HBr)
Chemical Formula: C12H14BrCl2N3O2
Exact Mass: 380.96
Molecular Weight: 383.070
Elemental Analysis: C, 37.63; H, 3.68; Br, 20.86; Cl, 18.51; N, 10.97; O, 8.35
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Related CAS #: 1232840-87-7 (free base) 1232841-78-9 (HBr) 2387898-69-1 (mesylate)
Synonym: PBT434 Hydrobromide; PBT 434; PBT-434; PBT434; ATH434; ATH-434; ATH 434;
IUPAC/Chemical Name: 5,7-Dichloro-2-((ethylamino)methyl)-8-hydroxy-3-methylquinazolin-4(3H)-one hydrobromide
InChi Key: WNTSHYWJAPIRQE-UHFFFAOYSA-N
InChi Code: InChI=1S/C12H13Cl2N3O2.BrH/c1-3-15-5-8-16-10-9(12(19)17(8)2)6(13)4-7(14)11(10)18;/h4,15,18H,3,5H2,1-2H3;1H
SMILES Code: O=C1N(C)C(CNCC)=NC2=C1C(Cl)=CC(Cl)=C2O.[H]Br
Appearance: To be determined
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: To be determined
Shelf Life: >2 years if stored properly
Drug Formulation: To be determined
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: ATH434 reduced oligomeric and urea soluble α-synuclein aggregation, reduced the number of GCIs, and preserved SNpc neurons. In vitro experiments suggest that ATH434 prevents the formation of toxic oligomeric "species of synuclein". ATH434 was able to prevent the development of hyposmia in young tau-/- mice, which coincided with a reduction in bulbar iron and copper levels, an increase in synaptophysin, and a reduction in soluble α-synuclein. ATH434 was able to prevent the development of motor impairment in aged tau-/- mice, which coincided with a reduction in iron levels and reduced neurodegeneration in the substantia nigra. ATH434 can reverse some of the GI deficits and enteric neuropathy that occur in a mouse model of PD, and thus may have potential clinical benefit in alleviating the GI dysfunctions associated with PD. ATH434-treated mice demonstrated preservation of motor performance in MSA mice that was associated with neuroprotection of nigral and striatal neurons. The rescue of the phenotype correlated with the reduction of α-syn inclusions and oligomers in animals receiving ATH434. ATH434-treated mice exhibited significantly increased lysosomal activity of microglia without increased pro-inflammatory markers, suggesting a role in α-syn clearing. ATH434-treatment was associated with lower intracellular nigral iron levels.
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The following data is based on the product molecular weight 383.07 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 |
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| In vivo protocol: |
1: Beauchamp LC, Liu XM, Vella LJ, Adlard PA, Bush AI, Finkelstein DI, Barnham KJ. ATH434 Rescues Pre-motor Hyposmia in a Mouse Model of Parkinsonism. Neurotherapeutics. 2022 Oct;19(6):1966-1975. doi: 10.1007/s13311-022-01300-0. Epub 2022 Sep 29. PMID: 36175781; PMCID: PMC9723006.
2: Finkelstein DI, Shukla JJ, Cherny RA, Billings JL, Saleh E, Stefanova N, Barnham KJ, Adlard PA. The Compound ATH434 Prevents Alpha-Synuclein Toxicity in a Murine Model of Multiple System Atrophy. J Parkinsons Dis. 2022;12(1):105-115. doi: 10.3233/JPD-212877. PMID: 34744051; PMCID: PMC9028676.
3: Diwakarla S, McQuade RM, Constable R, Artaiz O, Lei E, Barnham KJ, Adlard PA, Cherny RA, Di Natale MR, Wu H, Chai XY, Lawson VA, Finkelstein DI, Furness JB. ATH434 Reverses Colorectal Dysfunction in the A53T Mouse Model of Parkinson's Disease. J Parkinsons Dis. 2021;11(4):1821-1832. doi: 10.3233/JPD-212731. PMID: 34366375; PMCID: PMC8609706.
4: Heras-Garvin A, Refolo V, Schmidt C, Malfertheiner K, Wenning GK, Bradbury M, Stamler D, Stefanova N. ATH434 Reduces α-Synuclein-Related Neurodegeneration in a Murine Model of Multiple System Atrophy. Mov Disord. 2021 Nov;36(11):2605-2614. doi: 10.1002/mds.28714. Epub 2021 Jul 8. PMID: 34236731.
