PH-002 (PH002) is a novel and potent inhibitor of apolipoprotein (apo) E4 intramolecular domain interaction in neuronal cells and has the potential to be used to treat or prevent AD related to apoE4. Apolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer disease (AD) and likely contributes to neuropathology through various pathways. PH-002 restores mitochondrial cytochrome c oxidase subunit 1 levels, rescuing impairments of mitochondrial motility and neurite outgrowth.
Physicochemical Properties
| Molecular Formula | C27H33N5O4 |
| Molecular Weight | 491.58202624321 |
| Exact Mass | 491.253 |
| CAS # | 1311174-68-1 |
| Related CAS # | 1311174-68-1; |
| PubChem CID | 71451956 |
| Appearance | White to off-white solid powder |
| LogP | 2.7 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 36 |
| Complexity | 838 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | GSXXTLWPQMHHDJ-UHFFFAOYSA-N |
| 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) |
| 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 |
| Synonyms | PH002 PH 002 PH-002 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| 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]. |
| 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]. |
| 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 |
Solubility Data
| Solubility (In Vitro) | DMSO : ≥ 75 mg/mL (~152.57 mM) |
| 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 |