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Art. -Nr.: HY-188196

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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: no Target protein ligand; Blue: VHL E3 ligase ligand; Black: linker).

Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.

Formel: C₂₁₈H₃₂₁BF₁₂N₆₀O₅₄S₃
Molecular Weight:4981.24

Speicherung:

Please store the product under the recommended conditions in the Certificate of Analysis.

PVtCD-cTP-AlkF-2 Chemical Structure

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
Reinheit & Dokumentation
Verweise
Calculators
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

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^[1]. (Pink: no Target protein ligand; Blue: VHL E3 ligase ligand; Black: linker).

IC₅₀ & Target

^[1]

DAPK1

Alle PROTACs Isoform-spezifische Produkte anzeigen :

In Vitro

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.

Western Blot Analysis^[1]

Cell Line:

SH-SY5Y human neuroblastoma cells
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.

In Vivo

PVtCD-cTP-AlkF-2 (100 μM; i.v.; administered five times on days 0-12; until day 30) reduces DAPK1 and AD-like pathology and rescues cognitive deficits in aged APP/PS1 mice^[1].
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.

Animal Model:

APP/PS1 transgenic (aged 12-month-old)^[1]
Dosage:

100 μM, 100 μL
Administration:

i.v.; five doses on days 0, 3, 6, 9, and 12; until day 30
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.

Animal Model:

Aβ42 oligomer‑lesioned mice (established by stereotaxic hippocampal injection of Cy5‑labelled Aβ42 oligomers (100 μM, 100 μL))^[1]
Dosage:

1.8 mg/kg (100 μM, 100 μL)
Administration:

i.v.; five doses on days 0, 3, 6, 9, and 12; until day 30
Result:

Produced age-dependent DAPK1 degradation in the Aβ42 oligomer-induced AD mouse model, achieving 81% DAPK1 reduction in aged mice.

Related Protocols :

Chemical Information

Molecular Weight 4981.24
Formel C₂₁₈H₃₂₁BF₁₂N₆₀O₅₄S₃
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
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

Please store the product under the recommended conditions in the Certificate of Analysis.

Reinheit & Dokumentation

Handling Instructions (2659 KB)

Verweise

[1]. Peng L, et al. Blood-Brain Barrier-Permeable Macrocyclic Chimeras (BmTACs) for Targeted Protein Degradation in the Aging Brain. J Am Chem Soc. 2026.

Calculators

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Bioz

Keywords

MOQ

Minimum order quantity

100 mg

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