| Size | Price | |
|---|---|---|
| 10mg |
| Targets |
GlyT1 (glycine transporter-1, SLC6A9). PF-03463275 competitively and reversibly inhibits GlyT1 with a Ki of 11.6-13 nM, increasing synaptic glycine concentrations in the brain. This potentiation of NMDA receptor function is the proposed mechanism for cognitive enhancement in schizophrenia.
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|---|---|
| ln Vitro |
PF-03463275 inhibits human GlyT1 with a Ki of 11.6-13 nM in radioligand uptake assays. It demonstrates selectivity over GlyT2 and other neurotransmitter transporters. The compound reduces oscillatory potentials of the electroretinogram in rats, indicating functional CNS activity.
|
| ln Vivo |
Optic potentials (OPs) are attenuated by PF-03463275 (1–10 mg/kg; sc)[2].
Oral administration of PF-03463275 in rats results in significant brain penetration and GlyT1 inhibition. The compound has been shown to reduce oscillatory potentials in the electroretinogram at doses producing relevant plasma exposure. It is being investigated for cognitive impairment associated with schizophrenia. |
| Enzyme Assay |
GlyT1 uptake assays use cells expressing human GlyT1 incubated with radiolabeled glycine in the presence of test compounds. Uptake is measured by scintillation counting. Ki values are determined from competition curves using Cheng-Prusoff equation.
|
| Cell Assay |
Cell-based functional assays use GlyT1-expressing cells loaded with fluorescent glycine indicators, and uptake is measured by fluorescence microscopy. Glycine concentration-dependent NMDA receptor currents are recorded in hippocampal slices using electrophysiology.
|
| Animal Protocol |
Animal/Disease Models: Male SD (Sprague-Dawley) rats[2]
Doses: 1, 3 and 10 mg/kg Route of Administration: Sc Experimental Results: A dose-dependent reduction in the amplitude of oscillatory potentials (OPs) elicited from the dark-adapted rats. Rats receive PF-03463275 orally at various doses, and brain and plasma concentrations are measured by LC-MS/MS. Electroretinogram recordings assess the effect on oscillatory potentials. Cognitive behavioral tests such as novel object recognition and attentional set-shifting are used to evaluate potential cognitive enhancement. |
| References |
|
| Additional Infomation |
PF-03463275 has been used in research trials investigating the treatment of schizophrenia and cognitive impairment associated with schizophrenia.
|
| Molecular Formula |
C19H22N4OFCL.HCL
|
|---|---|
| Molecular Weight |
413.31652
|
| Exact Mass |
376.146
|
| CAS # |
1173177-11-1
|
| PubChem CID |
44156901
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
2.4
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
26
|
| Complexity |
526
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CN1C[C@H]2[C@@H](C1)[C@@H]2CN(CC3=CC(=C(C=C3)F)Cl)C(=O)C4=CN(C)C=N4.Cl.Cl
|
| InChi Key |
KYLOBHXXQOZRKK-YIONKMFJSA-N
|
| InChi Code |
InChI=1S/C19H22ClFN4O/c1-23-7-13-14(8-23)15(13)9-25(19(26)18-10-24(2)11-22-18)6-12-3-4-17(21)16(20)5-12/h3-5,10-11,13-15H,6-9H2,1-2H3/t13-,14+,15?
|
| Chemical Name |
N-[(3-chloro-4-fluorophenyl)methyl]-1-methyl-N-[[(1R,5S)-3-methyl-3-azabicyclo[3.1.0]hexan-6-yl]methyl]imidazole-4-carboxamide
|
| Synonyms |
PF 03463275 PF03463275 PF-03463275
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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 | 2.4194 mL | 12.0972 mL | 24.1943 mL | |
| 5 mM | 0.4839 mL | 2.4194 mL | 4.8389 mL | |
| 10 mM | 0.2419 mL | 1.2097 mL | 2.4194 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.
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