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).
For research use only. We do not sell to patients.
- Formula: C218H321BF12N60O54S3
- Molecular Weight:4981.24
-
Storage:
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]
-
Biological Activity
-
Chemical Information
- Protocols
- Purity & Documentation
- References
-
Help & FAQs
All PROTACs Isoforms
More
Biological Activity
Description
IC50 & Target
[1]|
DAPK1 |
In Vitro
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.
-
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 (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.
Chemical Information
-
Molecular Weight 4981.24
-
Formula 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
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PVtCD-cTP-AlkF-2 Related Classifications
HY-188196 Related Classifications
Powered by Bioz