| Chemical Properties | Back Directory | [Boiling point ]
626.880±65.00 °C(Press: 760.00 Torr)(predicted) | [density ]
1.439±0.10 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted) | [form ]
Solid | [pka]
-2.380±0.10(predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
MTX115325 (Example 1) is an orally active, brain-penetrating USP30 inhibitor (IC50=12 nM) with neuroprotective activity. MTX115325 increases ubiquitination (EC50=32 nM) of the mitochondrial outer membrane protein TOM20 (a USP30 substrate), increasing mitophagy. MTX115325 prevents dopaminergic neuron loss and preserves striatal dopamine[1]. | [in vivo]
MTX115325 (i.g.; 15 mg/kg and 50 mg/kg; twice daily for 10 weeks) reduces phosphorylated S129-αSyn levels and decreases the total area of GFAP staining in AAV-A53T-SNCA Mouse Model, indicating lower astrocyte activation[1].
MTX115325 (i.g.; 10 mg/kg; single dose) demonstrates excellent oral bioavailability (98%) and good CNS penetration with a brain partition coefficient (Kpu,u) of approximately 0.4[1].
MTX115325 (i.g.; single dose) has a Cmax of 7546.9 ng/mL at 15 mg/kg and a Cmax of 16374.3 ng/mL at 50 mg/kg. At a 50 mg/kg dosage, the drug concentration consistently remained above the EC50 for TOM20 ubiquitination[1]. | Animal Model: | AAV-A53T-SNCA Mouse Model [1] | | Dosage: | 15 mg/kg and 50 mg/kg | | Administration: | i.g.; twice daily for 10 weeks | | Result: | Reduced the loss of dopaminergic neurons in the substantia nigra (SN) and preserved dopamine levels in the striatum.
Increased the percentage of tyrosine hydroxylase (TH)+ neurons. |
| [References]
[1] Fang TZ et al. Knockout or inhibition of USP30 protects dopaminergic neurons in a Parkinson's disease mouse model. Nat Commun. 2023 Nov 13;14(1):7295. DOI:10.1038/s41467-023-42876-1 |
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| Company Name: |
NewCan Biotech Limited
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| Tel: |
+86-0571-86912261 +86-15658003402 |
| Website: |
https://www.newcanbio.com/ |
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