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| Size | Price | Stock |
|---|---|---|
| 50mg | $1550 | Check With Us |
| 100mg | $2250 | Check With Us |
| 200mg | $3375 | Check With Us |
: Cat #: V4442 CAS #: 1818339-66-0 (free base) Purity ≥ 98%
Description: PF-06751979 (PF06751979) is a novel, highly potent, brain penetrant, and selective inhibitor of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) with the potential to be used for the treatment of Alzheimer's disease. It inhibits BACE1 with an IC50 of 7.3 nM in BACE1 binding assay. PF-06751979 displays excellent brain penetration, potent in vivo efficacy, and broad selectivity over related aspartyl proteases including BACE2. Chronic dosing of 64 for up to 9 months in dog did not reveal any observation of hair coat color (pigmentation) changes and suggests a key differentiator over current BACE1 inhibitors that are nonselective against BACE2 in later stage clinical development. A major challenge in the development of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors for the treatment of Alzheimer's disease is the alignment of potency, drug-like properties, and selectivity over related aspartyl proteases such as Cathepsin D (CatD) and BACE2. The potential liabilities of inhibiting BACE2 chronically have only recently begun to emerge as BACE2 impacts the processing of the premelanosome protein (PMEL17) and disrupts melanosome morphology resulting in a depigmentation phenotype.
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| Molecular Weight (MW) | 455.4988 |
|---|---|
| Molecular Formula | C18H19F2N5O3S2 |
| CAS No. | 1818339-66-0 (free base) |
| Storage | -20℃ for 3 years in powder formr |
| -80℃ for 2 years in solvent | |
| SMILES Code | [H][C@@]12[C@@](CO[C@@H](C)C2)(C3=NC(NC(C4=NC=C(OC(F)F)C=C4)=O)=CS3)N=C(N)SC1 |
| Synonyms | PF06751979; PF 06751979; PF-06751979 |
| Protocol | 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. 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 |
|---|---|---|
| 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 dos |
| Solvent volume to be added | Mass (the weight of a compound) | |||
|---|---|---|---|---|
| Mother liquor concentration | 1mg | 5mg | 10mg | 20mg |
| 1mM | 2.1954 mL | 10.9770 mL | 21.9540 mL | 43.9079 mL |
| 5mM | 0.4391 mL | 2.1954 mL | 4.3908 mL | 8.7816 mL |
| 10mM | 0.2195 mL | 1.0977 mL | 2.1954 mL | 4.3908 mL |
| 20mM | 0.1098 mL | 0.5488 mL | 1.0977 mL | 2.1954 mL |
This equation is commonly abbreviated as: C1 V1 = C2 V2
- (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
- (2) Be sure to add the solvent(s) in order.