APY-d3
Based on 1 Customer Validation
APY-d3 is a highly selective EphA4 receptor inhibitor, with an IC50 value of 17-56 nM for human EphA4, an IC50 value of 20 nM for mouse EphA4, and a Kd value of 138 nM for EphA4-LBD. APY-d3 binds to EphA4, blocks its interaction with ephrin ligands, inhibits tyrosine phosphorylation of EphA4, prevents growth cone collapse, and does not induce EphA4 phosphorylation in primary cortical neurons. APY-d3 adopts a β-hairpin conformation stabilized by an N-terminal to C-terminal disulfide bond. APY-d3 can be used in research related to amyotrophic lateral sclerosis, Alzheimer's disease, stroke, neurodegenerative diseases and cancer.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 99.18%
- Fòrmula: C63H86N16O17S2
- Peso molecular:1403.58
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Almacenamiento:
Sealed storage, away from moisture.
Powder -80°C, 2 years , -20°C, 1 year* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
Actividad biológica
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EPHA4 17-56 nM (IC50) |
EphA4-LBD 138 nM (Kd) |
APY-d3 (0-72 h) potently inhibits ephrin-A5 binding to mouse and human EphA4 with IC50 values of 20 nM and 17 nM respectively, exhibits a plasma half-life of >72 hours, maintains activity in rat CSF for >72 hours, and is over 100-fold selective for EphA4 over other Eph receptors[1].
APY-d3 binds to the purified EphA4 LBD with an average KD of 27 nM[1].
APY-d3 inhibits ephrin-A5-induced EphA4 tyrosine phosphorylation in transfected HEK293 cells with an IC50 of 0.24 μM[1].
APY-d3 (15-30 μM; 24 h) is non-toxic to HT22 neuronal cells at concentrations up to 30 μM after 24 hours of incubation[1].
APY-d3 (150-200 nM) inhibits EphA4 phosphorylation by 30-40% in ephrin-A5-stimulated HEK293 cells[2].
APY-d3 (150-200 nM) completely inhibits growth cone collapse in retinal explants[2].
APY-d3 (0.1-100 nM; ~1 hour) potently inhibits ephrin-A5 AP binding to immobilized EphA4 Fc with an average IC50 of 20 nM, with modest reductions in potency in the presence of serum albumin[3].
APY-d3 (20-minute pre-incubation; 10-minute stimulation) inhibits ephrin-A5 Fc-induced EphA4 tyrosine phosphorylation in HEK-EphA4 cells with an IC50 of 130 nM[3].
APY-d3 (more than 72 hours) exhibits high protease resistance, with an in vitro plasma half-life of more than 72 hours[3].
APY-d3 (40 μM) binds to purified EphA4-LBD with a Kd of 138 nM as measured by isothermal titration calorimetry[4].
APY-d3 adopts a rigid, folded conformation in solution, as evidenced by increased chemical shift dispersion in its 1D 1H NMR spectrum[4].
APY-d3 induces chemical shift perturbations of Met115 in the GH loop of 13Cε-Met-labeled EphA4-LBD, with minimal effects on Met164 in the JK loop, as measured by 2D [13C, 1H] HSQC NMR spectroscopy[4].
APY-d3 binds to EphA4-LBD in a stabilized β-hairpin conformation, as revealed by X-ray crystallography (PDB ID 5JR2)[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HT22 neuronal cells
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Concentration:15 μM; 30 μM
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Incubation Time:24 h
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Result:Showed no evidence of cytotoxicity at concentrations 100-fold higher than its IC50 for EphA4 activation inhibition, with viable cell counts comparable to vehicle-treated controls.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (male, adult, 10-12 weeks old, photothrombotic ischemic stroke induced in forelimb motor cortex)[2]
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Dosage:5 mM
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Administration:i.c.v.; 0.25 μl/h; 14 days (starting 48 hours post-stroke)
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Result:Showed motor performance on accelerating rotarod and horizontal ladder task comparable to inactive peptide-treated mice after 2 weeks of treatment.
Did not enhance functional recovery compared to inactive peptide control, regardless of housing condition.
Demonstrated improved rotarod performance from day 35 post-stroke onward when housed in enriched environment, with no significant difference compared to inactive peptide-treated mice in enriched housing.
Maintained rotarod performance at ~70% of baseline in standard housing, similar to inactive peptide-treated mice in standard housing.
Showed no difference in horizontal ladder task foot fault rates compared to inactive peptide groups at any time point.
Reached mean brain concentrations of 150 nM in contralesional hemisphere and 530 nM in ipsilesional hemisphere at day 13 post-pump implantation, with one ipsilesional sample measuring up to 1200 nM.
Chemical Information
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Appearance Solid
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Peso molecular 1403.58
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Fòrmula C63H86N16O17S2
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Color White to off-white
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Sequence
{β-Ala}-Pro-Tyr-Cys-Val-Tyr-Arg-{β-Ala}-Ser-Trp-Ser-Cys (Disulfide bridge: Cys3-Cys10)
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Sequence Shortening
{β-Ala}-PYCVYR-{β-Ala}-SWSC (Disulfide bridge: Cys3-Cys10)
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Sealed storage, away from moisture
Powder -80°C 2 years -20°C 1 year * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvente y solubilidad
DMSO : 100 mg/mL (71.25 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Pureza y Documentación
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Ficha de datos (290 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Olson EJ, et al. Modifications of a Nanomolar Cyclic Peptide Antagonist for the EphA4 Receptor To Achieve High Plasma Stability. ACS medicinal chemistry letters. 2016 Sep 08;7(9):841-6. [Content Brief]
[2]. de Boer A, et al. Environmental enrichment during the chronic phase after experimental stroke promotes functional recovery without synergistic effects of EphA4 targeted therapy. Human molecular genetics. 2020 Mar 13;29(4):605-617. [Content Brief]
[3]. Gomez-Soler M, et al. Lipidation and PEGylation Strategies to Prolong the Half-Life of a Nanomolar EphA4 Receptor Antagonist. European journal of medicinal chemistry. 2023 Dec 15;262:115876. [Content Brief]
[4]. Prentiss AM, et al. Constrained β-Hairpins Targeting the EphA4 Ligand Binding Domain. Journal of medicinal chemistry. 2024 Dec 26;67(24):22245-22253. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 0.7125 mL | 3.5623 mL | 7.1246 mL | 17.8116 mL |
| 5 mM | 0.1425 mL | 0.7125 mL | 1.4249 mL | 3.5623 mL | |
| 10 mM | 0.0712 mL | 0.3562 mL | 0.7125 mL | 1.7812 mL | |
| 15 mM | 0.0475 mL | 0.2375 mL | 0.4750 mL | 1.1874 mL | |
| 20 mM | 0.0356 mL | 0.1781 mL | 0.3562 mL | 0.8906 mL | |
| 25 mM | 0.0285 mL | 0.1425 mL | 0.2850 mL | 0.7125 mL | |
| 30 mM | 0.0237 mL | 0.1187 mL | 0.2375 mL | 0.5937 mL | |
| 40 mM | 0.0178 mL | 0.0891 mL | 0.1781 mL | 0.4453 mL | |
| 50 mM | 0.0142 mL | 0.0712 mL | 0.1425 mL | 0.3562 mL | |
| 60 mM | 0.0119 mL | 0.0594 mL | 0.1187 mL | 0.2969 mL |
APY-d3 Related Classifications
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