E2072
E2072 is a selective, orally active competitive inhibitor of glutamate carboxypeptidase II (GCPII) with a Ki of 10 nM. E2072 alleviates established thermal hyperalgesia in a rat model of chronic constriction injury. E2072 prevents oxaliplatin-induced reductions in nerve conduction velocity and amplitude in mice. E2072 is applicable to research related to neuropathic pain and neuropathy.
For research use only. We do not sell to patients.
- CAS No.: 378242-00-3
- Formula: C16H14O4S
- Molecular Weight:302.34
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
In Vitro
E2072 (50-200 nM) potently and competitively inhibits recombinant human GCPII with a Ki of 10 nM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
| Species | Dose | Route | Cmax | Tmax | AUCinf | Clearance (CL) | Vd | T1/2 | CL/F | Vd/F | F | AUC0-inf | T1/2 (Absorption) | T1/2 (Elimination) | Bioavailability |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 10 mg/kg | i.v. | 57226 ng/mL | 0.11 h | / | / | / | / | / | / | / | 86973 ng·h/mL | 0.87 h | 105 h | 38 % |
| Monkey[2] | 5 mg/kg | i.v. | 68013.3 ng/mL | 0.08 h | 63622.1 ng·h/mL | 0.022 L/h/kg | 0.72 L/kg | 23 h | / | / | / | / | / | / | / |
| Monkey[2] | 5 mg/kg | p.o. | 10454.3 ng/mL | 0.42 h | 24935.6 ng·h/mL | / | / | 9.57 h | 0.057 L/h/kg | 0.79 L/kg | 39.1 % | / | / | / | / |
In Vivo
E2072 (administered via oral gavage, once daily for 4 consecutive weeks at doses of 0.01-1.0 mg/kg) prevents oxaliplatin (HY-17371)-induced reductions in nerve conduction velocity and amplitude in female BALB/c mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (male, 200-250 g, chronic constrictive injury model)[1]
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Dosage:10 mg/kg; 1 mg/kg; 0.1 mg/kg; 0.01 mg/kg
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Administration:p.o.; daily; up to 11 consecutive days
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Result:Significantly attenuated pre-existing thermal hyperalgesia with 10, 1, or 0.1 mg/kg doses, with significant reductions observed from the eighth day of treatment.
Prolonged analgesic effect for up to 7 days after cessation of 10 mg/kg treatment.
Showed no effect on hyperalgesia at 0.01 mg/kg dose.
Did not alter normal thermal sensitivity in nonligated paws.
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Animal Model:BALB/c (female, ~20 g, oxaliplatin-induced model)[1]
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Dosage:1 mg/kg; 0.1 mg/kg; 0.01 mg/kg
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Administration:p.o.; daily; 4 weeks
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Result:Significantly prevented oxaliplatin-induced caudal nerve conduction velocity deficits at 0.01, 0.1, and 1.0 mg/kg doses (Oxaliplatin alone reduced caudal NCV to 88% of control).
Significantly prevented oxaliplatin-induced digital nerve conduction velocity deficits at 0.1 and 1.0 mg/kg doses (Oxaliplatin alone reduced digital NCV to 90.58% of control).
Prevented oxaliplatin-induced caudal and digital amplitude deficits at 0.1 and 1.0 mg/kg doses (Oxaliplatin alone reduced caudal amplitude to 83 % of control and digital amplitude to 79% of control).
Did not prevent digital velocity or amplitude deficits at 0.01 mg/kg dose.
Chemical Information
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CAS No. 378242-00-3
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Molecular Weight 302.34
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Formula C16H14O4S
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SMILES
O=C(O)C=1C=CC=C(C1)C=2C=CC=C(C2C(=O)O)CCS
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Cardiac voltage-sensitive optical mapping
Cardiac voltage-sensitive optical mapping records changes in transmembrane potential from cardiac tissue by staining the preparation with a voltage-sensitive dye and imaging fluorescence changes during electrical activation; the resulting optical action potentials can be used to map activation time, action potential duration, conduction velocity, wavefront propagation, and arrhythmia dynamics. The optical signal represents a relative fluorescence change from a tissue volume rather than a single-cell intracellular recording, so spatial resolution, sampling rate, voltage resolution, optical magnification, light penetration, and motion control must be considered together when interpreting optical action potentials.
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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
Purity & Documentation
References
[1]. Wozniak KM, et al. The orally active glutamate carboxypeptidase II inhibitor E2072 exhibits sustained nerve exposure and attenuates peripheral neuropathy. J Pharmacol Exp Ther. 2012;343(3):746-754. [Content Brief]
[2]. Rais R, et al. Reversible disulfide formation of the glutamate carboxypeptidase II inhibitor E2072 results in prolonged systemic exposures in vivo. Drug Metab Dispos. 2012;40(12):2315-2323. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)