| Size | Price | Stock | Qty |
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| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
PF-06648671 targets γ-secretase as a modulator rather than a full inhibitor. It selectively inhibits the production of amyloid-β (1-42) (Aβ42) in CHO cells expressing wild-type amyloid precursor protein (APP; IC50 = 9.8 nM) over Notch cleavage to its signaling effector Notch intracellular domain (NICD; IC50 >15.8 µM). This selectivity spares Notch signaling while reducing Aβ42 and Aβ40 production.
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| ln Vitro |
PF-06648671 increased Aβ37 and Aβ38 while decreasing Aβ42 and Aβ40 in cell-based experiments, all without preventing Notch or other substrate cleavage [1].
In vitro, PF-06648671 reduces Aβ42 and Aβ40 production with concomitant increases in Aβ37 and Aβ38. In CHO cells expressing wild-type APP, it selectively inhibits Aβ42 production with an IC50 of 9.8 nM. Importantly, it shows minimal inhibition of Notch cleavage to NICD (IC50 >15.8 µM), demonstrating over 1,600-fold selectivity. |
| ln Vivo |
It has been demonstrated that PF-06648671 decreases Aβ42 in the brain and CSF following acute oral treatment in mice [1].
In vivo, PF-06648671 demonstrates reduction of Aβ42 within the brain and cerebrospinal fluid (CSF) following acute oral administration in animal models. Its brain penetration and oral bioavailability support its utility for studying Alzheimer's disease. The compound has been studied in preclinical and clinical settings as a disease-modifying therapy. |
| Enzyme Assay |
Specific cell-free enzyme/receptor binding assay protocols for PF-06648671 involve γ-secretase activity assays. Aβ42 production inhibition (IC50 = 9.8 nM) and Notch cleavage inhibition (IC50 >15.8 µM) are measured using cell-free or cell-based assays with appropriate substrates. Selectivity for Aβ42 over Notch signaling is confirmed through these assays.
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| Cell Assay |
In vitro cell-based assays for PF-06648671 use CHO cells expressing wild-type amyloid precursor protein (APP). Cells are treated with the compound, and Aβ peptide levels (Aβ42, Aβ40, Aβ37, Aβ38) are measured in culture supernatants using ELISA or mass spectrometry. Notch signaling is assessed by measuring NICD production.
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| Animal Protocol |
In vivo animal studies for PF-06648671 have been conducted in animal models of Alzheimer's disease. Acute oral administration reduces Aβ42 levels within the brain and CSF. The compound's brain penetration and target engagement are confirmed through pharmacokinetic and pharmacodynamic studies. These studies support its potential as a disease-modifying therapy.
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| ADME/Pharmacokinetics |
PF-06648671 has a molecular formula of C25H23ClF4N4O3 and a molecular weight of 538.92 g/mol. It is a solid powder with purity ≥95%. The compound is orally active and brain-penetrant. Storage: powder at -20°C. The IUPAC name is 2-[(1S)-1-[(2S,5R)-5-[4-chloro-5-fluoro-2-(trifluoromethyl)phenyl]oxolan-2-yl]ethyl]-7-(4-methylimidazol-1-yl)-3,4-dihydropyrido[1,2-a]pyrazine-1,6-dione.
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| Toxicity/Toxicokinetics |
Specific toxicological data for PF-06648671 are not detailed in the available literature. The compound is classified for research use only and is not intended for human therapeutic applications. As a γ-secretase modulator that spares Notch signaling, it is designed to have an improved safety profile compared to full γ-secretase inhibitors. Formal toxicological profiles are not extensively reported.
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| References | |
| Additional Infomation |
PF-06648671 (CAS 1587727-31-8) is a novel, brain-penetrant, orally active γ-secretase modulator (GSM) for Alzheimer's disease research. It selectively reduces Aβ42 and Aβ40 production (Aβ42 IC50 = 9.8 nM) while sparing Notch signaling (NICD IC50 >15.8 µM). The compound has been studied in preclinical and clinical settings. No approved indication data are available.
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| Molecular Formula |
C25H23CLF4N4O3
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|---|---|
| Molecular Weight |
538.921738862991
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| Exact Mass |
538.139
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| Elemental Analysis |
C, 55.72; H, 4.30; Cl, 6.58; F, 14.10; N, 10.40; O, 8.91
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| CAS # |
1587727-31-8
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| PubChem CID |
73441910
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| Appearance |
White to off-white solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
37
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| Complexity |
992
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC1=CN(C=N1)C2=CC=C3C(=O)N(CCN3C2=O)[C@@H](C)[C@@H]4CC[C@@H](O4)C5=CC(=C(C=C5C(F)(F)F)Cl)F
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| InChi Key |
AKCDDYGYIGPEKL-JQOQJDEVSA-N
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| InChi Code |
InChI=1S/C25H23ClF4N4O3/c1-13-11-32(12-31-13)19-3-4-20-24(36)33(7-8-34(20)23(19)35)14(2)21-5-6-22(37-21)15-9-18(27)17(26)10-16(15)25(28,29)30/h3-4,9-12,14,21-22H,5-8H2,1-2H3/t14-,21-,22+/m0/s1
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| Chemical Name |
2-[(1S)-1-[(2S,5R)-5-[4-chloro-5-fluoro-2-(trifluoromethyl)phenyl]oxolan-2-yl]ethyl]-7-(4-methylimidazol-1-yl)-3,4-dihydropyrido[1,2-a]pyrazine-1,6-dione
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| Synonyms |
PF06648671; PF 06648671; PF-06648671
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8556 mL | 9.2778 mL | 18.5556 mL | |
| 5 mM | 0.3711 mL | 1.8556 mL | 3.7111 mL | |
| 10 mM | 0.1856 mL | 0.9278 mL | 1.8556 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(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.
Link: https://clinicaltrials.gov/ct2/show/NCT02883114
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT02440100
Conditions:Healthy Adult Subjects and Healthy Elderly SubjectsLink: https://clinicaltrials.gov/ct2/show/NCT02407353
Conditions:Healthy Subjects
Title:A Single Ascending Dose Study To Evaluate Safety And Pharmacokinetics Of Compound PF-06648671 In Healthy Subjects
Status:Completed
updateDate:2015-06-09
Ctid:NCT02316756
Link: https://clinicaltrials.gov/ct2/show/NCT02316756
Conditions:Healthy SubjectsProducts are for research use only; We do not sell to patients
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