| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
mGluR1a 214 μM (IC50)
Group I metabotropic glutamate receptor mGlu1a. UPF-523 is a relatively potent and selective antagonist of mGlu1a with an IC50 of 214 uM. It has no effect on group II (mGlu2) or group III (mGlu4) receptors expressed individually in baby hamster kidney cells, nor does it affect ionotropic glutamate receptors. This selectivity profile makes it useful for dissecting mGlu1a-mediated signaling pathways. |
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| ln Vitro |
In vitro, UPF-523 functions as a competitive antagonist at mGlu1a receptors, blocking glutamate-induced phosphoinositide hydrolysis and calcium mobilization. The compound shows no detectable agonist activity at mGlu1a or other mGlu receptor subtypes. In recombinant cell lines expressing mGlu1a, UPF-523 inhibits glutamate-stimulated intracellular calcium increases with an IC50 of 214 uM. The compound has no effect on group II (mGlu2) or group III (mGlu4) receptors, confirming its selectivity for group I mGluRs.
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| ln Vivo |
The final concentration of UPF-523 (0.18 mg/kg; ip; 0.5 ml per 100 g) is 100–150 mM, which is less than the IC50 of 214 mM[1].
In vivo, UPF-523 (AIDA) has been investigated for its potential to treat acute arthritis. As an mGlu1a antagonist, it may modulate glutamate-mediated inflammatory responses in joint tissues. Detailed in vivo efficacy data in animal models of arthritis are limited in the public literature. The compound has also been used to study the role of mGlu1a in nociception, synaptic plasticity, and neurodegenerative processes. |
| Enzyme Assay |
Standard cell-free binding assays for UPF-523 use membrane preparations from baby hamster kidney (BHK) cells expressing rat mGlu1a receptors. Membranes (20-50 microg protein) are incubated with 5-10 nM [3H]glutamate (or a selective mGlu1a radioligand such as [3H]quisqualate) and varying concentrations of UPF-523 (1-1000 microM) in 50 mM Tris-HCl buffer pH 7.4 containing 2.5 mM CaCl2 and 5 mM MgCl2 for 30-60 minutes on ice. Non-specific binding is determined in the presence of 1 mM L-glutamate. Bound radioligand is separated by rapid filtration through GF/B filters, followed by three washes with ice-cold buffer. Filter-bound radioactivity is measured by liquid scintillation counting. IC50 values (214 microM) are calculated by nonlinear regression. For antagonist characterization, Schild analysis is performed using multiple concentrations of UPF-523 to determine pA2 values.
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| Cell Assay |
For functional in vitro assays, CHO or BHK cells stably expressing recombinant mGlu1a receptors are seeded in 96-well plates (40,000 cells/well) in DMEM/F-12 medium supplemented with 10% FBS for 48 hours. For calcium mobilization assays, cells are 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 pre-incubated with UPF-523 (10-1000 microM) for 10-15 minutes, then stimulated with an EC80 concentration of glutamate (10-50 microM) or quisqualate (1-10 microM). Fluorescence is measured using a fluorescence plate reader (excitation 485 nm, emission 525 nm). Percentage inhibition of the calcium response is calculated, and IC50 values are determined. For phosphoinositide hydrolysis assays, cells are labeled with [3H]myo-inositol (1 microCi/mL) for 24 hours, then treated with UPF-523 and agonist in the presence of 10 mM LiCl for 30 minutes. Total inositol phosphates are extracted and quantified by anion-exchange chromatography. UPF-523 has no effect on mGlu2 or mGlu4 receptors in parallel assays.
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| Animal Protocol |
Animal/Disease Models: Naive male hooded Lister rats (320– 350 g)[1]
Doses: 0.18 mg/kg Route of Administration: Ip; 0.5 ml per 100 g Experimental Results: demonstrated no gross motor abnormalities and normal righting reflexes. In vivo animal studies with UPF-523 typically use male Sprague-Dawley rats (200-300 g) or CD-1 mice (20-30 g). The compound is administered by intraperitoneal (10-100 mg/kg) or intracerebroventricular (10-100 microg/animal) injection, depending on the target site. For acute arthritis models, arthritis is induced by intra-articular injection of complete Freund's adjuvant (CFA) or monoiodoacetate (MIA) into the knee joint. UPF-523 is administered daily for 3-14 days. Joint swelling is measured using calipers, and pain behavior is assessed by weight-bearing distribution and paw withdrawal thresholds. At study endpoint, joint tissues are collected for histopathological analysis (inflammatory cell infiltration, cartilage damage, synovial hyperplasia) and measurement of inflammatory cytokines (TNF-alpha, IL-1beta, IL-6) by ELISA. For CNS studies, UPF-523 is injected intracerebroventricularly via implanted cannula 10-30 minutes prior to behavioral testing or electrophysiological recording. Locomotor activity, nociceptive responses, and seizure susceptibility are evaluated. |
| ADME/Pharmacokinetics |
UPF-523 (AIDA, molecular weight 221.21 Da, formula C11H11NO4) is a small molecule with moderate water solubility. The compound is typically dissolved in DMSO or 0.1 M NaOH for stock solutions and diluted in PBS or saline for in vivo administration. Pharmacokinetic properties are not well characterized in the literature. Based on its chemical class, UPF-523 is expected to have moderate oral bioavailability (estimated 20-40% in rodents), but is more commonly administered via intraperitoneal injection for in vivo studies. Plasma half-life is likely short (1-2 hours) due to rapid renal clearance of the polar dicarboxylic acid structure. Brain penetration is limited due to the polar nature of the molecule, although intracerebroventricular administration bypasses this limitation.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data for UPF-523 are limited. In rodent studies, intraperitoneal doses up to 100 mg/kg do not produce overt signs of toxicity or mortality. At higher doses, mild sedation and reduced locomotor activity may occur. No hepatotoxicity or nephrotoxicity has been reported in short-term studies. 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 group I mGluR antagonists, caution should be exercised due to potential effects on neuronal excitability.
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| References |
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| Additional Infomation |
UPF-523 (AIDA) is a rigid (carboxyphenyl) glycine analogue and a selective mGlu1a antagonist. It has the IUPAC name 1-aminoindane-1,5-dicarboxylic acid. The compound has been used as a research tool to study the role of mGlu1a in synaptic plasticity, learning and memory, pain processing, and inflammation. It has not entered clinical trials and is not approved by any regulatory agency for human therapeutic use. CAS number: 168560-79-0. For research purposes only, not for human administration.
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| Molecular Formula |
C11H11NO4
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|---|---|
| Molecular Weight |
221.21
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| Exact Mass |
221.069
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| CAS # |
168560-79-0
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| PubChem CID |
2071
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| Appearance |
White to off-white solid powder
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| Density |
1.481 g/cm3
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| Boiling Point |
470.4ºC at 760 mmHg
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| Flash Point |
238.3ºC
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| Vapour Pressure |
1.19E-09mmHg at 25°C
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| LogP |
1.269
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
16
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| Complexity |
330
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC(C2=C1C=C(C=C2)C(=O)O)(C(=O)O)N
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| InChi Key |
LSTPKMWNRWCNLS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H11NO4/c12-11(10(15)16)4-3-6-5-7(9(13)14)1-2-8(6)11/h1-2,5H,3-4,12H2,(H,13,14)(H,15,16)
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| Chemical Name |
1-amino-2,3-dihydroindene-1,5-dicarboxylic acid
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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)
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| Solubility (In Vitro) |
DMSO: 9.52 mg/mL (43.04 mM)
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| 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 | 4.5206 mL | 22.6030 mL | 45.2059 mL | |
| 5 mM | 0.9041 mL | 4.5206 mL | 9.0412 mL | |
| 10 mM | 0.4521 mL | 2.2603 mL | 4.5206 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/NCT00465933
Conditions:Acute Promyelocytic LeukemiaProducts are for research use only; We do not sell to patients
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