| Identification | Back Directory | [Name]
3,6,9-Trioxa-12,15-diazahexadecanamide, 15-[4-(4-acetylhexahydro-1H-1,4-diazepin-1-yl)-6-[[2-(2-thienyl)ethyl]amino]-1,3,5-triazin-2-yl]-N-[(1S)-1-[[(2R,4S)-4-hydroxy-2-[[[[4-(4-methyl-5-thiazolyl)phenyl]methyl]amino]carbonyl]-1-pyrrolidinyl]carbonyl]-2,2-dimethylpropyl]-13-oxo- | [CAS]
2417159-57-8 | [Synonyms]
C004019
3,6,9-Trioxa-12,15-diazahexadecanamide, 15-[4-(4-acetylhexahydro-1H-1,4-diazepin-1-yl)-6-[[2-(2-thienyl)ethyl]amino]-1,3,5-triazin-2-yl]-N-[(1S)-1-[[(2R,4S)-4-hydroxy-2-[[[[4-(4-methyl-5-thiazolyl)phenyl]methyl]amino]carbonyl]-1-pyrrolidinyl]carbonyl]-2,2-dimethylpropyl]-13-oxo- | [Molecular Formula]
C49H70N12O9S2 | [MOL File]
2417159-57-8.mol | [Molecular Weight]
1035.29 |
| Hazard Information | Back Directory | [Uses]
C004019 is a BBB-penatrable and small-molecule PROTAC that targets tau. C004019 can simultaneously recruit tau and E3 ligase, and effectively clear tau proteins by promoting the ubiquitination and proteasome-dependent degradation of tau, thereby improving synaptic and cognitive functions in Alzheimer's disease (AD) mice. C004019 can be used in the research of AD and tau protein-related diseases. (Pink: Ligand for target protein (HY-138679); Black: linker (HY-140189); Blue: E3 Ligase Ligand (HY-138678))[1] | [in vivo]
C004019 (intracerebroventricular injection; 5 μL; 200 μM; single dose) reduces the level of tau protein in the brains of wild-type and 3xTg-AD mice[1].
C004019 (subcutaneous injection; 3-15 mg/kg; single dose) effectively clears tau protein in the brains of wild-type mice[1].
C004019 (subcutaneous injection; 3 mg/kg; once every 6 days for five times) promotes tau clearance and improves cognitive and synaptic functions in hTau and 3xTg-AD mice[1]. | Animal Model: | hTau transgenic mice aged 12 months old[1] | | Dosage: | 3 mg/kg | | Administration: | Subcutaneous injection (s.c.); once every 6 days for a total of 5 times | | Result: | Significantly reduced total and p-tau levels in the hippocampal extracts.
Reduced both soluble and insoluble tau, more efficiently to the tau in the soluble fraction.
Ameliorated cognitive functions and dentritic plasticity in hTau transgenic mouse model.
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| Animal Model: | 3xTg-AD mice aged 9.5 months old[1] | | Dosage: | 3 mg/kg | | Administration: | Subcutaneous injection (s.c.); once every 6 days for a total of 5 times | | Result: | Remarkably reduced both soluble and insoluble tau levels in hippocampal and cortex extracts, more efficiently to the tau in the soluble fraction.
Significantly reduced T22-positive tau in the soluble fraction.
Improved the cognitive and synaptic functions in 3xTg-AD mice.
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| [References]
[1] Wang W, et al. A novel small-molecule PROTAC selectively promotes tau clearance to improve cognitive functions in Alzheimer-like models. Theranostics. 2021 Mar 11;11(11):5279-5295. DOI:10.7150/thno.55680 |
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