CPP-115 hydrochloride
CPP-115 hydrochloride is an orally active, selective GABA-AT inhibitor with a Ki value of 9.7 μM. CPP-115 hydrochloride blocks GABA degradation and increases GABA levels in the brain. CPP-115 hydrochloride does not bind to GABA transporters, does not displace GABA from GABAA/GABAB receptors, and does not act as an agonist/antagonist of GABAC receptors. CPP-115 hydrochloride reduces cocaine-induced dopamine release, blocks cocaine-induced conditioned place preference, and suppresses seizure activity in a rat model of infantile spasms. CPP-115 hydrochloride can be used in research related to infantile spasms and epilepsy.
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- CAS. Nr.: 760947-97-5
- Formel: C7H10ClF2NO2
- Molecular Weight:213.61
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biologische Aktivität
Beschreibung
In Vitro
CPP-115 hydrochloride potently and irreversibly inactivates GABA-AT with a kinact/KI of 52 mM·min-1, 187 times more efficiently than vigabatrin[1].
CPP-11 (6 mM) hydrochloride does not exhibit inhibitory or inactivating activity against alanine aminotransferase or aspartate aminotransferase at concentrations up to 6 mM[1].
CPP-115 (0-4.0 equiv; up to 120 h) hydrochloride time-dependently inactivates pig brain GABA-AT with a turnover number of 1.3 per active site, with greater inactivation observed at higher equivalents of the compound[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
CPP-115 (1 mg/kg) hydrochloride reduces cocaine-induced dopamine release in the nucleus accumbens (NAcc) of rats to 250% of the basal level, and its potency is over 300 times higher than that of Vigabatrin[1].
CPP-115 (0.1-1 mg/kg) hydrochloride suppresses seizure episodes in the adrenocorticotropic hormone (ACTH)-resistant multi-hit infantile spasm rat model, with a potency 100-fold higher than that of Vigabatrin and better tolerability[1].
CPP-115 (20 mg/kg per day for 45 consecutive days) hydrochloride causes only 5%-30% loss of electroretinogram in rats after 45 days of administration, showing extremely low retinal toxicity compared to the effective dose of Vigabatrin[1].
CPP-115 (0.7-7 mg/kg/day; p.o.; daily; 28 days) hydrochloride is well tolerated in healthy Beagle dogs[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:unspecified[1]
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Dosage:1 mg/kg
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Administration:administered with cocaine during training
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Result:Eliminated cocaine-induced conditioned place preference, with rats spending 7.8 minutes in the cocaine-paired chamber and 7.2 minutes in the unpaired chamber (comparable to saline/saline control levels).
Did not produce place preference alone.
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Animal Model:unspecified[1]
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Dosage:1 mg/kg
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Administration:administered to modulate cocaine-induced dopamine release
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Result:Reduced cocaine-induced nucleus accumbens dopamine level increase from 550% of basal levels to 250% of basal levels.
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Animal Model:unspecified[1]
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Dosage:0.5 mg/kg
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Administration:administered with cocaine
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Result:Prevented displacement of [11C]-raclopride in the nucleus accumbens, indicating insufficient dopamine release to displace the tracer.
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Animal Model:unspecified[1]
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Dosage:20 mg/kg/day
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Administration:daily; 45 days
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Result:Resulted in only 5-30% electroretinographic loss, a dose that is 20-40 times higher than the effective infantile spasms dose of 0.5-1 mg/kg/day.
Chemical Information
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CAS. Nr. 760947-97-5
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Molecular Weight 213.61
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Formel C7H10ClF2NO2
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SMILES
OC([C@H]1C/C([C@H](C1)N)=C(F)\F)=O.Cl
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Protokoll
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How to Select a Suitable Non-Mouse Animal Model
Selecting a suitable non-mouse animal model is a structured decision based on the research question, required anatomy or physiology, disease mechanism, endpoint feasibility, translational relevance, and ethical justification. Non-mouse models are preferred when mice cannot reproduce key human-relevant features, such as organ size, surgical anatomy, cardiovascular physiology, neuroanatomy, immune features, pharmacology, toxicology, or long-term clinical procedures. Candidate species may include rats, rabbits, guinea pigs, ferrets, zebrafish, pigs, sheep, goats, dogs, cats, horses, and non-human primates, but each species must be justified by its specific scientific advantage rather than convenience or tradition. Unresolved questions include how to quantify translational superiority across species, how to balance increased biological relevance against higher ethical burden, and when human-derived systems or new approach methodologies should replace animal use.
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How to Choose the Right Model Animal
Choosing the right model animal is a validity-driven decision in which the species, strain, sex, age, genetic background, disease-induction method, outcome measures, and welfare burden must match the scientific question rather than laboratory tradition or convenience. A model should be selected by judging face validity, construct validity, and predictive validity: whether it resembles the human phenotype, whether it reproduces relevant mechanisms, and whether results are likely to predict human biology or treatment response. Animal studies often fail to translate because of species differences, weak disease resemblance, poor experimental design, inadequate reporting, publication bias, and underuse of randomization, blinding, and sample-size justification. Unresolved questions include how to rank competing models objectively, how much human-disease complexity must be reproduced for a given objective, and when non-animal systems such as organoids, ex vivo tissue, or computational models
Reinheit & Dokumentation
Verweise
[1]. Silverman RB. The 2011 E. B. Hershberg award for important discoveries in medicinally active substances: (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a GABA aminotransferase inactivator and new treatment for drug addiction and infantile spasms. J Med Chem. 2012 Jan 26;55(2):567-75. [Content Brief]
[2]. Lee H, et al. Mechanism of inactivation of γ-aminobutyric acid aminotransferase by (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115). Journal of the American Chemical Society. 2015 Feb 25;137(7):2628-40. [Content Brief]
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)