MTK458

• CAT Number: I041728
• CAS Number: 2499962-58-0
• Molecular Formula: C17H15F3N4
• Molecular Weight: 332.32
• Purity: ≥95%
• Synonyms: N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-6-(trifluoromethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine
• InChI: InChI=1S/C17H15F3N4/c18-17(19,20)14-8-12-15(21-9-22-16(12)24-14)23-13-7-3-5-10-4-1-2-6-11(10)13/h1-2,4,6,8-9,13H,3,5,7H2,(H2,21,22,23,24)/t13-/m1/s1
• InChIKey: JOIONRWKOGDQOG-CYBMUJFWSA-N
• SMILES: C1CC(C2=CC=CC=C2C1)NC3=NC=NC4=C3C=C(N4)C(F)(F)F

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].
MTK458 (25 µM) increases PINK1-mediated mitophagy to enhance clearance of intramitochondrial aggregates in Hela cells induced ΔOTC and YFP-Parkin[1].
MTK458 (0.1-25 µM) clears pS129 α-synuclein aggregates (12-250 kDa) in a dose-dependent manner in DIV9 and DIV12[1].
MTK458 (0-13 µM, 10 days) reduces α-synuclein pathology and the mitochondrial stress marker pUb in iPSC neurons[1].
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].

Reference

[1]. Chin RM, et al. Pharmacological PINK1 activation ameliorates Pathology in Parkinson’s Disease models. bioRxiv [Preprint]. 2023 Feb 15:2023.02.14.528378.
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