PVtCD-cTP-AlkF-2
PVtCD-cTP-AlkF-2 is a ROS-responsive DAPK1 BmTAC activator with blood-brain barrier permeability. PVtCD-cTP-AlkF-2 is equipped with a VHL E3 ubiquitin ligase ligand modified with a ROS-responsive phenylboronic acid caging group, and undergoes uncaging activation only in a high-ROS microenvironment. PVtCD-cTP-AlkF-2 can selectively recognize and degrade dephosphorylated activated DAPK1. PVtCD-cTP-AlkF-2 exerts its activator function through caveolae-mediated transcytosis. PVtCD-cTP-AlkF-2 reduces APP and Tau phosphorylation, decreases Aβ oligomer deposition, and improves cognitive function in aged APP/PS1 mice. PVtCD-cTP-AlkF-2 can be used for research on Alzheimer's disease.
(Pink: DAPK1 ligand (HY-P12376); Blue: VHL E3 ligase ligand; Black: linker (HY-22408)).
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 分子式: C218H321BF12N60O54S3
- 分子量:4981.24
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
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生物活性
製品説明
IC50 & Target
[1]|
DAPK1 |
体外実験
PVtCD-cTP-AlkF-2 (100 μM H2O2; 24 h) is stable at pH 7.4 but undergoes nearly complete ROS-responsive decaging[1].
PVtCD-cTP-AlkF-2 (2.5-20 μM; 0-36 h) reduced total DAPK1 by 62% and selectively degraded activated DAPK1 through proteasome- and ROS-dependent mechanisms, thereby reversing downstream APP and Tau phosphorylation in Aβ42 oligomer-exposed SH-SY5Y cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:SH-SY5Y human neuroblastoma cells
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Concentration:0, 2.5, 5, 10, 20 μM (dose-dependent)
10 μM (time-dependent) -
Incubation Time:24 h
0, 6, 12, 24, 36 h -
Result:Degraded DAPK1 protein in Aβ42 oligomer-treated SH-SY5Y cells in a dose-dependent and time-dependent manner, while p-DAPK1(Ser308) remains largely unaffected.
体内実験
PVtCD-cTP-AlkF-2 (1.8 mg/kg; i.v.; five injections on days 0-12; up to day 30) produces age-dependent DAPK1 degradation in the Aβ42 oligomer-induced AD mouse model, achieving 81% DAPK1 reduction in aged mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:APP/PS1 transgenic (aged 12-month-old)[1]
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Dosage:100 μM, 100 μL
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Administration:i.v.; five doses on days 0, 3, 6, 9, and 12; until day 30
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Result:Achieved a 55% reduction in DAPK1 protein levels.
Degraded DAPK1 predominantly in NeuN-positive neurons.
Did not significantly alter phosphorylated DAPK1 (Ser308) or CaMKII protein levels.
Suppressed APP and Tau phosphorylation markedly.
Reduced Aβ oligomer deposition significantly.
Showed preserved neuronal morphology and increased Nissl body content in hippocampus and cortex by Nissl staining.
Showed a significantly greater proportion of swimming distance in the target quadrant in Morris water maze.
Enhanced nest-building quality.
Identified 100 upregulated and 74 downregulated proteins by proteomic analysis, enriched in pathways governing neuron survival, autophagy, energy metabolism, inflammation, and synaptic plasticity.
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Animal Model:Aβ42 oligomer‑lesioned mice (established by stereotaxic hippocampal injection of Cy5‑labelled Aβ42 oligomers (100 μM, 100 μL))[1]
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Dosage:1.8 mg/kg (100 μM, 100 μL)
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Administration:i.v.; five doses on days 0, 3, 6, 9, and 12; until day 30
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Result:Produced age-dependent DAPK1 degradation in the Aβ42 oligomer-induced AD mouse model, achieving 81% DAPK1 reduction in aged mice.
化学情報
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分子量 4981.24
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分子式 C218H321BF12N60O54S3
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SMILES
OC1=CC=C(C[C@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@H](CCCCN)NC([C@@H](CC2)CC[C@@H]2C(N[C@H](C(N3[C@@H](C[C@H](C3)OC(OCC4=CC=C(B(O)O)C=C4)=O)C(NCC5=CC=C(C6=C(C)N=CS6)C=C5)=O)=O)C(C)(C)C)=O)=O)=O)CCCCN)=O)CC(N)=O)=O)CCCNC(N)=N)=O)CC(N)=O)=O)CCCCN)=O)CC(C)C)=O)CCCNC(N)=N)=O)CCCNC(N)=N)=O)CCC(N)=O)=O)CC7=CNC=N7)=O)CO)=O)C(NCCCCCC(N[C@H]8CSC(C9=O)CC(N9CCC(OCC(F)(C(F)(C(F)(C(F)(C(F)(C(F)(COC(CCN%10C(CC(C%10=O)SC[C@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC8=O)CC%11=CNC=N%11)=O)CC(C)C)=O)CC(N)=O)=O)[C@H](CC)C)=O)CC(C)C)=O)CO)=O)[C@@H](C)O)=O)CC(C)C)=O)CC%12=CNC%13=CC=CC=C%13%12)=O)CCCCN)=O)CC%14=CC=C(O)C=C%14)=O)CCCNC(N)=N)=O)C(N)=O)=O)=O)F)F)F)F)F)F)=O)=O)=O)=O)C=C1
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
PVtCD-cTP-AlkF-2 関連分類
HY-188196 関連分類
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