| Description | PF-06751979 is an inhibitor of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) (IC50 of 7.3 nM in BACE1 binding assay). |
| In vitro | PF-06751979 shows improved selectivity over BACE2 (IC50=194 nM) in binding (27-fold) relative to the literature examples and across multiple chemical series in BACE1 program. |
| In vivo | PF-06751979 displays excellent brain penetration, potent in vivo efficacy, and broad selectivity over related aspartyl proteases including BACE2. Acute administration of PF-06751979 yields a robust dose-responsive and time-dependent reduction of cerebral spinal fluid (CSF) Aβx-40 with peak inhibition at 3 h of >77%.[1]. |
| Target activity | BACE1:7.3 nM , BACE2:194 nM |
| molecular weight | 455.5 |
| Molecular formula | C18H19F2N5O3S2 |
| CAS | 1818339-66-0 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | Ethanol: 50 mg/mL (109.77 mM), Sonication is recommended. DMSO: 150 mg/mL (329.31 mM), Sonication is recommended. |
| References | 1. O'Neill BT, et al. Design and Synthesis of Clinical Candidate PF-06751979: A Potent, Brain Penetrant, β-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitor Lacking Hypopigmentation. J Med Chem. 2018 May 24;61(10):4476-4504. |