PF-06751979 是一种有效的，脑渗透性的 β-淀粉样前体蛋白裂解酶1 (BACE1) 抑制剂，IC₅₀ 为 7.3 nM。

PF-06751979 is a potent, brain penetrant, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor with an IC 50 of 7.3 nM in BACE1 binding assay.

Solid

IC50: 7.3 nM (BACE1), 194 nM (BACE2)

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. PF-06751979 also inhibits BACE1 and BACE2 in a fluorescent polarization (FP) assay with IC50s of 26.9 nM and 238 nM, respectively. PF-06751979 has excellent potency at BACE1 in binding or FP assay formats along with cellular activity looking at production of sAPPβ in H4 cells with an IC50 of 5 nM. has not independently confirmed the accuracy of these methods. They are for reference only.

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%. To determine if the reduction in brain and CSF Aβ is maintained during sustained exposure to PF-06751979, a 5 day subchronic study is executed, dosing once daily by subcutaneous (SC) administration (10 or 50 mg/kg/day). Brain and CSF samples are collected on day 5, following the last dose. PF-06751979 produces a dose-responsive and time-dependent inhibition of Aβ42 in mouse brain. At the 50 mg/kg/day dose, maximal brain lowering is 63% at 7 to 9 h. Administration of PF-06751979 (10 or 50 mg/kg/day for 5 days) produces a dose-responsive and time-dependent inhibit

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. ONeill 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.

In Vitro: DMSO : 150 mg/mL (329.31 mM; Need ultrasonic)Ethanol : 50 mg/mL (109.77 mM; Need ultrasonic)配制储备液