| Identification | Back Directory | [Name]
7H-Pyrrolo[2,3-d]pyrimidin-4-amine, N-[(1R)-1,2,3,4-tetrahydro-1-naphthalenyl]-6-(trifluoromethyl)- | [CAS]
2499962-58-0 | [Synonyms]
Mitophagy activator 1
MTK458 EP-0035985
7H-Pyrrolo[2,3-d]pyrimidin-4-amine, N-[(1R)-1,2,3,4-tetrahydro-1-naphthalenyl]-6-(trifluoromethyl)- | [Molecular Formula]
C17H15F3N4 | [MOL File]
2499962-58-0.mol | [Molecular Weight]
332.32 |
| Chemical Properties | Back Directory | [density ]
1.422±0.06 g/cm3(Predicted) | [solubility ]
DMSO: Sparingly soluble: 1-10 mg/ml | [form ]
Solid | [pka]
10.59±0.50(Predicted) | [color ]
White to yellow |
| Hazard Information | Back Directory | [Uses]
MTK458 is an orally active brain penetrant PINK1 activator. MTK458 binds to PINK1 and stabilizes an active heterocomplex, thereby increasing mitophagy. MTK458 can be used for research on Parkinson's disease[1]. | [in vivo]
MTK458 (50 mg/kg, p.o., daily, 6 months) drives clearance of pathologic α-synuclein in a dose-dependent manner in the stratum of mice injected with α-synuclein preformed fibrils (PFFs)[1].
MTK458 (50 mg/kg, p.o., 6 doses, 5 days) decreases plasma pS65-Ubiquitin (pUb) in wild-type Sprague-Dawley rats[1].
| Animal Model: | Stratum of mice injected with α-synuclein preformed fibrils (PFFs)[1] | | Dosage: | 50 mg/kg | | Administration: | Oral gavage (p.o.), daily, 6 months | | Result: | Rescued an activity deficit in freely moving PFF mice.
Reduced the levels of inflammatory markers (TREM2, IL-6, and CXCL1).
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| Animal Model: | C57BL6J wildtype mice injected with PFF [1] | | Dosage: | 50 mg/kg | | Administration: | Oral gavage (p.o.); 7 days, 3 weeks | | Result: | Decreased pUb in the brain and plasma of PFF seeded mice.
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| [References]
[1] Chin RM, et al. Pharmacological PINK1 activation ameliorates Pathology in Parkinson's Disease models. bioRxiv [Preprint]. 2023 Feb 15:2023.02.14.528378. DOI:10.1101/2023.02.14.528378 |
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