| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
GlyT1 (glycine transporter-1).
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|---|---|
| ln Vitro |
PF-03463275 is a potent and selective GlyT1 inhibitor with a Ki of 11.6 nM. It is a competitive and reversible inhibitor. By inhibiting GlyT1, it increases synaptic glycine levels, which enhances NMDA receptor function. The compound has a LogP of 2.4 and is CNS-permeable.
|
| ln Vivo |
Optic potentials (OPs) are attenuated by PF-03463275 (1–10 mg/kg; sc)[2].
In vivo, PF-03463275 (1-10 mg/kg; subcutaneous injection) attenuates optic potentials (OPs) in a dose-dependent manner in male Sprague-Dawley rats. It has been used in clinical trials for the treatment of schizophrenia and cognitive impairments associated with schizophrenia. |
| Enzyme Assay |
In vitro receptor binding assays for PF-03463275 are performed to evaluate its affinity for GlyT1. Radioligand binding studies using membrane preparations from cells expressing GlyT1 are conducted. The compound's ability to displace a specific radiolabeled GlyT1 ligand is measured to calculate its Ki value (11.6 nM).
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| Cell Assay |
In vitro cell-based assays are conducted using cells expressing recombinant GlyT1. The cells are treated with PF-03463275, and the inhibition of glycine uptake is measured to quantify the compound's inhibitory activity. The selectivity of PF-03463275 for GlyT1 over other transporters is confirmed by testing its activity against GlyT2 and other related transporters.
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| 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. In vivo animal studies are conducted in rodent models to evaluate the effects of PF-03463275 on GlyT1-mediated neurotransmission and behavior. The compound is typically administered via subcutaneous injection at doses of 1, 3, and 10 mg/kg. Its effects on optic potentials and cognitive function are assessed. |
| ADME/Pharmacokinetics |
PF-03463275 is an orally bioactive compound with CNS permeability. Detailed pharmacokinetic parameters such as half-life, bioavailability, and brain-to-plasma ratio are not extensively documented in publicly available literature. Its LogP is 2.4.
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| Toxicity/Toxicokinetics |
No specific toxicity data are publicly available for PF-03463275. As a GlyT1 inhibitor, its toxicity profile is expected to be related to its mechanism of action. Standard safety precautions should be followed when handling this compound.
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| References |
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| Additional Infomation |
PF-03463275 has been used in research trials investigating the treatment of schizophrenia and cognitive impairment associated with schizophrenia.
PF-03463275 is a potent, selective, and CNS-penetrant GlyT1 inhibitor that has been investigated for the treatment of schizophrenia and cognitive impairments. It is an orally bioactive compound that enhances NMDA receptor function by increasing synaptic glycine levels. The compound is not approved for human therapeutic use and is strictly for research purposes. |
| Molecular Formula |
C19H22CLFN4O
|
|---|---|
| Molecular Weight |
376.86
|
| Exact Mass |
448.099
|
| CAS # |
1173239-39-8
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| PubChem CID |
44156901
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| 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)C2CN(CC3=CC(=C(C=C3)F)Cl)C(=O)C4=CN(C=N4)C
|
| 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
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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)
|
| Solubility (In Vitro) |
DMSO: 33.33 mg/mL (88.44 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.83 mg/mL (2.20 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.83 mg/mL (2.20 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 0.83 mg/mL (2.20 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6535 mL | 13.2675 mL | 26.5351 mL | |
| 5 mM | 0.5307 mL | 2.6535 mL | 5.3070 mL | |
| 10 mM | 0.2654 mL | 1.3268 mL | 2.6535 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/NCT01911676
Conditions:Cognitive Impairments Associated With SchizophreniaLink: https://clinicaltrials.gov/ct2/show/NCT00977522
Conditions:SchizophreniaLink: https://clinicaltrials.gov/ct2/show/NCT01159626
Conditions:Healthy
Title:A Study Of Adjunctive Treatment Of Cognitive Deficits In Schizophrenia
Status:Completed
updateDate:2008-10-02
Ctid:NCT00567203
Link: https://clinicaltrials.gov/ct2/show/NCT00567203
Conditions:SchizophreniaProducts are for research use only; We do not sell to patients
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