PH-002

PH-002 is an inhibitor of the interaction between the amino- and carboxy-terminal domains of apolipoprotein E4 (ApoE4, IC50 = 116 nM in a FRET reporter assay for domain interaction). It restores intracellular trafficking of ApoE4 to the endoplasmic reticulum and Golgi apparatus in Neuro-2a cells expressing EGFP-ApoE4 or EGFP-ApoE4-R61T, a mutation that impairs ApoE4 domain interactions, when used at a concentration of 100 nM. PH-002 also prevents impairments in neurite outgrowth and dendritic spine development induced by expression of ApoE4 in Neuro-2a cells. It restores levels of mitochondrial complex IV subunit 1 in Neuro-2a cells expressing ApoE4 (EC50 = 39 nM) and increases mitochondrial motility in PC12 cells expressing ApoE4 (EC50 = <1 nM).Formal Name: 4-[[4-[[2-(3,4-dihydro-3-methyl-4-oxo-1-phthalazinyl)acetyl]amino]phenyl]methyl]-1-piperazinecarboxylic acid, 1,1-dimethylethyl ester. CAS Number: 1311174-68-1. Molecular Formula: C27H33N5O4. Formula Weight: 491.6. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMF: 15mg/mL, DMF:PBS (pH 7.2) (1:9): 0.1mg/mL, DMSO: 10mg/mL, Ethanol: 10mg/mL. lambdamax: 248 nm. SMILES: O=C(OC(C)(C)C)N1CCN(CC2=CC=C(NC(CC3=NN(C)C(C4=C3C=CC=C4)=O)=O)C=C2)CC1. 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). InChi Key: GSXXTLWPQMHHDJ-UHFFFAOYSA-N.