[CAS NO. 1818339-66-0] PF-06751979
PRODUCTS SPECIFICATIONS [1818339-66-0]
DESCRIPTION [1818339-66-0]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 455.50 |
| Molecular Formula | C18H19F2N5O3S2 |
| SMILES | FC(F)OC1=CN=C(C(NC2=CSC([C@]34CO[C@@H](C)C[C@@]3([H])CSC(N)=N4)=N2)=O)C=C1 |
1 Publications Citing Use of MCE
Summary
IC50 & Target
IC50: 7.3 nM (BACE1), 194 nM (BACE2) [1]
In Vitro
PF-06751979 shows improved selectivity over BACE2 (IC 50 =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 IC 50 s 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 IC 50 of 5 nM [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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%. 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 inhibition of Aβx-40 in mouse CSF resulting in 77% inhibition of CSF at 3 h post-final 50 mg/kg dose [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT02793232 | Pfizer |
Healthy Subjects
|
June 13, 2016 | Phase 1 |
| NCT02509117 | Pfizer |
Healthy Subjects
|
July 2015 | Phase 1 |
| NCT03126721 | Pfizer |
Healthy
|
April 18, 2017 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 150 mg/mL ( 329.31 mM ; Need ultrasonic)
Ethanol : 50 mg/mL ( 109.77 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.1954 mL | 10.9769 mL | 21.9539 mL |
| 5 mM | 0.4391 mL | 2.1954 mL | 4.3908 mL |
| 10 mM | 0.2195 mL | 1.0977 mL | 2.1954 mL |
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Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.75 mg/mL (6.04 mM); Clear solution
