| Identification | Back Directory | [Name]
4(3H)-Quinazolinone, 5,7-dichloro-2-[(ethylamino)methyl]-8-hydroxy-3-methyl-, methanesulfonate (1:1) | [CAS]
2387898-69-1 | [Synonyms]
ATH-434
PBT434 methanesulfonate
PBT434 mesylate (Synonyms: ATH434 mesylate)
4(3H)-Quinazolinone, 5,7-dichloro-2-[(ethylamino)methyl]-8-hydroxy-3-methyl-, methanesulfonate (1:1) | [Molecular Formula]
C13H17Cl2N3O5S | [MOL File]
2387898-69-1.mol | [Molecular Weight]
398.26 |
| Hazard Information | Back Directory | [Uses]
PBT434 methanesulfonate is a potent, orally active and cross the blood-brain barrier α-synuclein aggregation inhibitor. PBT434 methanesulfonate can be used as a iron chelator and modulates transcellular iron trafficking. PBT434 methanesulfonate inhibits iron-mediated redox activity and iron-mediated aggregation of α-synuclein. PBT434 methanesulfonate prevents the loss of substantia nigra pars compacta neurons (SNpc). PBT434 methanesulfonate has the potential for the research of Parkinson’s disease (PD)[1][2]. | [in vivo]
PBT434 methanesulfonate (30 mg/kg; p.o.; daily for 21 days) significantly preserved neuron numbers in the 6-OHDA intoxication model and shows significantly fewer rotations in the L-DOPA model, significantly reducing SNpc neuronal loss in the MPTP model[1]. | Animal Model: | 12 weeks, 25 g, Male C57BL/6 J mice (6-OHDA intoxication model)[1] | | Dosage: | 30 mg/kg | | Administration: | P.o.; daily for 21 days (commencing 3 days following induction of lesion) | | Result: | Prevented neuronal loss following 6-OHDA, preserving up to 75% of the SNpc neurons remaining (both Nissl and tyrosine hydroxylase (TH) positive neurons) after the initial phase of cell death. |
| Animal Model: | 12 weeks, 25 g, Male C57BL/6 J mice (MPTP model)[1] | | Dosage: | 1, 3, 10, 30, 80 mg/kg | | Administration: | P.o.; daily for 21 days (commenced 24?h after induction of lesion) | | Result: | Increased the proportion of SNpc cells rescued, increased there was a trend to improved turning behavior, significantly increased varicosity abundance, prevented the decline in levels of the presynaptic marker synaptophysin (SYNP) in a dose-dependent manner. |
| [IC 50]
α-synuclein Aggregation | [References]
[1] Finkelstein DI, et al. The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson's disease. Acta Neuropathol Commun. 2017 Jun 28;5(1):53. DOI:10.1186/s40478-017-0456-2
[2] Bailey DK, Clark W, Kosman DJ. The iron chelator, PBT434, modulates transcellular iron trafficking in brain microvascular endothelial cells. PLoS One. 2021 Jul 26;16(7):e0254794. DOI:10.1371/journal.pone.0254794 |
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