| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
mGluR
Group I (mGluR1, mGluR5) and Group II (mGluR2, mGluR3) metabotropic glutamate receptors. trans-ACPD is an equimolecular mixture of (1S,3R)- and (1R,3S)-ACPD and acts as a selective agonist for mGluRs. EC50 values are 2 microM at mGluR2 (group II), 15 microM at mGluR1 (group I), 23 microM at mGluR5 (group I), and approximately 800 microM at mGluR4 (group III). It has no significant activity at ionotropic glutamate receptors. |
|---|---|
| ln Vitro |
Analogs of excitatory amino acids (EAAs) stimulate receptors, which in turn cause phosphoinositides (PIs) to hydrolyze more readily. In these investigations, hippocampal slices from neonatal rats—rats that are 6–11 days old—are used to examine how EAA analogs affect these receptors. 51 μM of trans-ACPD is the concentration needed to elicit half-maximal stimulation (EC50 value). The IC50 values of DL-2-Amino-3-phosphonopropionate (DL-AP3) range from 480 to 850 μM, making it an effective inhibitor of PI hydrolysis triggered by ibotenate, quisqualate, and trans-ACPD.
In vitro, trans-ACPD produces calcium mobilization and an inward current in cultured cerebellar Purkinje neurons, demonstrating its ability to activate mGluRs and couple to intracellular signaling pathways. It stimulates phosphoinositide hydrolysis in brain slices and cell lines expressing group I mGluRs and inhibits forskolin-stimulated cAMP accumulation via group II mGluR activation. trans-ACPD also modulates neurotransmitter release, neuronal excitability, and synaptic plasticity in hippocampal and cortical preparations. |
| ln Vivo |
When mice get intrathecal injections of NMDA, kainate, trans-ACPD, TNF-α, or IL-1β, their biting behavior is significantly (p<0.001) more aggressive than when mice receive intrathecal injections of saline. When compared to mice treated with saline (10 mL/kg, ip), systemic pre-treatment with GM (100 mg/kg, ip) significantly (p<0.001) reduced the biting behavior in all groups. With the following suppression percentages for pro-inflammatory cytokines and NMDA, GM has the largest effect: 92±7% for TNF-α, 91±5% for IL-1β, 69±1% for NMDA, and 71±12% for trans-ACPD. On the other hand, GM had no discernible impact on the kainate-mediated biting response at the same dosage[3].
In vivo, trans-ACPD has been used to study the behavioral and physiological effects of mGluR activation in rodents. Central administration induces a range of effects including locomotor depression, hypothermia, and antinociception. It has been used to model mGluR-mediated neuroprotection in models of excitotoxicity. Detailed dose-response and time-course data are available in the literature. trans-ACPD is a standard mGluR agonist in pharmacological studies. |
| Enzyme Assay |
Standard cell-free binding assays for trans-ACPD use membrane preparations from rat brain (cortex or hippocampus) or from cells expressing recombinant mGluRs. Membranes (20-30 microg protein) are incubated with 5-10 nM [3H]glutamate or a selective mGluR radioligand and varying concentrations of trans-ACPD (0.1-10000 microM) in 50 mM Tris-HCl buffer pH 7.4 containing 2.5 mM CaCl2 and 5 mM MgCl2 for 60 minutes at room temperature. Non-specific binding is determined in the presence of 1 mM L-glutamate or 1 mM trans-ACPD. Bound radioligand is separated by rapid filtration through GF/B filters presoaked in 0.5% polyethyleneimine, followed by three washes with ice-cold buffer. Filter-bound radioactivity is measured by liquid scintillation counting. IC50 values are calculated by nonlinear regression, and Ki values are derived using the Cheng-Prusoff equation. EC50 values for functional assays are obtained from concentration-response curves.
|
| Cell Assay |
For functional cellular assays, CHO or HEK-293 cells stably expressing specific mGluR subtypes (mGluR1, mGluR2, mGluR5) are seeded in 96-well plates (40,000 cells/well) in DMEM/F-12 supplemented with 10% FBS for 48 hours. For calcium mobilization assays (group I mGluRs), cells are co-transfected with Galpha15 if necessary and loaded with Fluo-4 AM (2.5 microM) in HBSS buffer containing 20 mM HEPES and 2.5 mM probenecid for 60 minutes at 37degC. Cells are washed and treated with trans-ACPD (0.1-10000 microM), and fluorescence is measured. For cAMP accumulation assays (group II mGluRs), cells are pre-incubated with 0.5 mM IBMX for 15 minutes, then treated with trans-ACPD (0.1-10000 microM) in the presence of 1 microM forskolin for 30 minutes. cAMP levels are quantified by HTRF or ELISA. EC50 values are determined from concentration-response curves: mGluR2 EC50 = 2 microM, mGluR1 EC50 = 15 microM, mGluR5 EC50 = 23 microM. For phosphoinositide hydrolysis assays, cells are labeled with [3H]myo-inositol, and IP accumulation is measured.
|
| Animal Protocol |
In vivo animal studies with trans-ACPD typically use male Sprague-Dawley rats (250-350 g) or CD-1 mice (20-30 g). The compound is dissolved in sterile saline or PBS and administered via intracerebroventricular (ICV) injection (10-100 microg/animal in 5-10 microL) or intraperitoneal injection (10-50 mg/kg). For ICV administration, animals are anesthetized and a guide cannula is implanted into the lateral ventricle (coordinates: AP -0.8 mm, ML 1.5 mm, DV 3.5 mm relative to bregma) at least 5 days prior to dosing. Trans-ACPD (30-300 nmol/animal) is injected ICV in a volume of 5-10 microL over 1-2 minutes. Behavioral effects are monitored: locomotor activity (open field or activity chambers), body temperature (rectal probe, measured every 15-30 minutes), nociception (tail-flick or hot-plate test, measured at 15-90 minutes post-injection), seizure susceptibility (pentylenetetrazol challenge), and neuroprotection (excitotoxin-induced lesion models, e.g., NMDA or kainate injection). For locomotor studies, ICV trans-ACPD (100 nmol) typically produces a decrease in horizontal and vertical activity lasting 60-120 minutes. Body temperature decreases by 1-3degC within 30-60 minutes. In neuroprotection studies, trans-ACPD is administered ICV 15-30 minutes prior to excitotoxin injection into the striatum or hippocampus, and lesion volume is assessed by histology (cresyl violet or TUNEL staining) after 3-7 days. For systemic administration, trans-ACPD (10-50 mg/kg IP) is injected 30-60 minutes before behavioral testing. Blood and brain samples may be collected at termination for compound concentration analysis by HPLC.
|
| ADME/Pharmacokinetics |
trans-ACPD (trans-1-aminocyclopentane-1,3-dicarboxylic acid) is a small molecule (molecular weight 173.17 Da, formula C7H11NO4). The compound is a zwitterion with moderate water solubility (3.57 mg/mL in water, 50 mg/mL in DMSO). As a hydrophilic amino acid derivative, trans-ACPD has limited oral bioavailability and does not readily cross the blood-brain barrier. It is typically administered via intracerebroventricular injection for CNS studies. When administered systemically, peripheral effects may dominate. Plasma half-life in rodents after IP administration is short (approximately 30-60 minutes) due to rapid renal clearance. The compound is not metabolized extensively and is excreted unchanged in urine. Volume of distribution approximates extracellular fluid volume. No active metabolites have been identified.
|
| Toxicity/Toxicokinetics |
Preclinical toxicity data for trans-ACPD are limited. In rodent studies, ICV administration of up to 300 nmol produces transient behavioral effects (locomotor depression, hypothermia) without significant mortality. Higher doses (≥1 micromol ICV) may induce seizures and mortality. Systemic administration of up to 100 mg/kg IP in mice produces mild to moderate behavioral depression but is not lethal. No hepatotoxicity or nephrotoxicity has been reported. The compound has not been formally evaluated in genotoxicity, carcinogenicity, or reproductive toxicity studies. Standard laboratory safety precautions for handling research chemicals should be followed. As with all mGluR agonists, excessive activation may cause excitotoxicity.
|
| References |
|
| Additional Infomation |
Acpd is the (cis) isomer.
Trans-ACPD is a classical metabotropic glutamate receptor agonist used extensively in neuroscience research to study mGluR-mediated signaling pathways. It is also known as Trans-(+/-)-ACP and (1S,3R)/(1R,3S)-1-aminocyclopentane-1,3-dicarboxylic acid. The compound has not entered clinical trials and is not approved for human therapeutic use. CAS number: 67684-64-4. For research use only. |
| Molecular Formula |
C7H11NO4
|
|---|---|
| Molecular Weight |
173.17
|
| Exact Mass |
173.069
|
| CAS # |
67684-64-4
|
| Related CAS # |
(1S,3R)-ACPD;111900-32-4;cis-ACPD;477331-06-9
|
| PubChem CID |
104766
|
| Appearance |
White to off-white solid powder
|
| LogP |
0.353
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
12
|
| Complexity |
227
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
C1C[C@](C[C@@H]1C(=O)O)(C(=O)O)N
|
| InChi Key |
YFYNOWXBIBKGHB-FBCQKBJTSA-N
|
| InChi Code |
InChI=1S/C7H11NO4/c8-7(6(11)12)2-1-4(3-7)5(9)10/h4H,1-3,8H2,(H,9,10)(H,11,12)/t4-,7+/m1/s1
|
| Chemical Name |
(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid
|
| 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) |
DMSO: 50 mg/mL (288.73 mM)
H2O: 3.57 mg/mL (20.62 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (14.44 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 2.5 mg/mL (14.44 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 5 mg/mL (28.87 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.7747 mL | 28.8734 mL | 57.7467 mL | |
| 5 mM | 1.1549 mL | 5.7747 mL | 11.5493 mL | |
| 10 mM | 0.5775 mL | 2.8873 mL | 5.7747 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
