| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
PH-002 targets the intramolecular domain interaction of ApoE4. By inhibiting this interaction, it restores mitochondrial cytochrome c oxidase subunit 1 levels, rescuing impairments of mitochondrial motility and neurite outgrowth. It has an IC50 of 116 nM in a FRET assay.
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| ln Vitro |
PH-002 has an IC50 of 116 nM in FRET and inhibits the intramolecular domain interaction of apolipoprotein (apo) E4 in neural cells [1].
In vitro, PH-002 inhibits the ApoE4 intramolecular domain interaction with an IC50 of 116 nM in a FRET-based assay. This suggests it can effectively disrupt the pathological conformation of ApoE4. |
| ln Vivo |
Additionally, it has been demonstrated that PH-002 raises COX1 levels in primary neurons found in the hippocampus and cortex of NSE-apoE4 transgenic mice. Following four days of PH-002 (200 nM) therapy, COX1 levels rose by almost 60%. The results of apoE3-expressing primary neurons treated with PH-002 are identical to unprocessed primary neurons. PH-002 (100 nM) enhances dendritic spine formation in primary neurons of NSE-apoE4 transgenic mice to levels equivalent to NSE-apoE3 primary neurons [2].
In vivo, PH-002 has the potential to rescue impairments of mitochondrial motility and neurite outgrowth in neuronal cells. By inhibiting the ApoE4 intramolecular domain interaction, it may restore normal neuronal function and prevent the neurodegeneration associated with ApoE4. |
| Enzyme Assay |
The in vitro assay for PH-002 measures its ability to inhibit the ApoE4 intramolecular domain interaction. This is typically performed using a FRET (Förster resonance energy transfer) assay, where the interaction is measured by the energy transfer between two fluorophores attached to different domains of the protein.
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| Cell Assay |
In vitro cell-based assays are performed in neuronal cell models expressing ApoE4. Cells are treated with PH-002, and the effect on mitochondrial motility, neurite outgrowth, and mitochondrial function is assessed. The restoration of cytochrome c oxidase subunit 1 levels is measured by Western blotting.
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| Animal Protocol |
In vivo activity would be evaluated in animal models of Alzheimer's disease that express human ApoE4. The compound would be administered, and its effect on cognitive function, neurodegeneration, and biomarkers of disease would be assessed.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of PH-002 are not detailed in the literature. As a research compound, its primary use is in vitro, and its in vivo PK properties would need to be determined for therapeutic development.
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| Toxicity/Toxicokinetics |
Toxicological data for PH-002 is not available. As a research compound, it is not intended for human use. Its safety profile would need to be established if it were to be developed further.
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| References |
[1]. Brodbeck J, et al. Structure-dependent impairment of intracellular apolipoprotein E4 trafficking and its detrimental effects are rescued by small-molecule structure correctors. J Biol Chem. 2011 May 13;286(19):17217-26.
[2]. Chen HK, et al. Small molecule structure correctors abolish detrimental effects of apolipoprotein E4 in cultured neurons. J Biol Chem. 2012 Feb 17;287(8):5253-66 |
| Additional Infomation |
PH-002 is a novel research tool for studying the role of ApoE4 in Alzheimer's disease. It represents a potential therapeutic strategy for a significant proportion of AD patients who carry the ApoE4 allele. It is not an approved drug.
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| Molecular Formula |
C27H33N5O4
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|---|---|
| Molecular Weight |
491.58202624321
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| Exact Mass |
491.253
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| CAS # |
1311174-68-1
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| Related CAS # |
1311174-68-1;
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| PubChem CID |
71451956
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| Appearance |
White to off-white solid powder
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| LogP |
2.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
36
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| Complexity |
838
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)(C)OC(=O)N1CCN(CC1)CC2=CC=C(C=C2)NC(=O)CC3=NN(C(=O)C4=CC=CC=C43)C
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| InChi Key |
GSXXTLWPQMHHDJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H33N5O4/c1-27(2,3)36-26(35)32-15-13-31(14-16-32)18-19-9-11-20(12-10-19)28-24(33)17-23-21-7-5-6-8-22(21)25(34)30(4)29-23/h5-12H,13-18H2,1-4H3,(H,28,33)
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| Chemical Name |
4-[[4-[[2-(3,4-Dihydro-3-methyl-4-oxo-1-phthalazinyl)acetyl]amino]phenyl]methyl]-1-piperazinecarboxylic acid 1,1-dimethylethyl ester
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| Synonyms |
PH002 PH 002 PH-002
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 75 mg/mL (~152.57 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.09 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0343 mL | 10.1713 mL | 20.3426 mL | |
| 5 mM | 0.4069 mL | 2.0343 mL | 4.0685 mL | |
| 10 mM | 0.2034 mL | 1.0171 mL | 2.0343 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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