| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg | |||
| 500mg | |||
| 1g | |||
| Other Sizes |
| Targets |
CGS20625 specifically targets the central benzodiazepine binding site of the GABAA receptor complex, where it acts as a partial agonist. GABAA receptors are pentameric ligand-gated chloride channels that mediate fast inhibitory neurotransmission in the central nervous system. The benzodiazepine binding site is located at the interface between the α and γ subunits of the GABAA receptor and modulates the receptor's response to GABA. CGS20625 exhibits high affinity for this site with an IC50 of 1.3 nM. As a partial agonist, the compound produces a GABA ratio of 0.9 and a 20% enhancement of TBPS binding, indicating a profile distinct from full benzodiazepine agonists such as diazepam. The compound shows subunit-dependent efficacy with highest activity at α1β2γ2 receptors.
|
|---|---|
| ln Vitro |
CGS20625 demonstrates potent in vitro activity at the central benzodiazepine receptor with an IC50 of 1.3 nM for inhibition of [³H]-flunitrazepam binding. The compound shows no affinity for several other neurotransmitter receptor binding sites, indicating a high degree of selectivity. As a partial agonist, CGS20625 enhances GABA responses in Xenopus oocytes expressing GABAA receptors, with a profile indicative of partial agonism including a GABA ratio of 0.9. The compound's partial agonist activity at the benzodiazepine site is responsible for its anxiolytic and anticonvulsant effects with reduced sedative and muscle relaxant side effects compared to full benzodiazepine agonists.
|
| ln Vivo |
In vivo, CGS20625 produces anxiolytic and anticonvulsant effects in animal models. The compound exhibits an oral ED50 of 0.7 mg/kg for anticonvulsant activity. Importantly, CGS20625 does not produce rotarod impairment at doses exceeding 300 times the anxiolytic dose, indicating a wide therapeutic window with minimal sedation and motor impairment. The compound lacks the muscle relaxation and ethanol potentiation effects associated with classical benzodiazepines. These properties make CGS20625 a valuable tool for studying the dissociation between anxiolytic and sedative effects of benzodiazepine site ligands. The compound has been studied in various animal models of anxiety and epilepsy.
|
| Enzyme Assay |
The binding affinity of CGS20625 to the central benzodiazepine receptor is assessed using radioligand binding assays. Membranes from rat brain tissue (typically cerebral cortex) are incubated with a radiolabeled benzodiazepine ligand, such as [³H]-flunitrazepam or [³H]-diazepam, in the presence of varying concentrations of the test compound. Nonspecific binding is determined using a competing benzodiazepine (e.g., diazepam or clonazepam). IC50 or Ki values are calculated from competition binding curves. Receptor selectivity is assessed by screening the compound against panels of other neurotransmitter receptors, ion channels, and transporters. Functional activity (agonist, partial agonist, or antagonist) is determined using electrophysiological recordings or [³⁵S]TBPS binding assays.
|
| Cell Assay |
Cellular assays for CGS20625 involve the use of cells expressing recombinant GABAA receptors, typically in Xenopus oocytes or mammalian cell lines. For Xenopus oocyte assays, oocytes are injected with cRNA encoding GABAA receptor subunits (e.g., α1, β2, γ2) and cultured for several days to allow receptor expression. Oocytes are then voltage-clamped, and GABA-evoked chloride currents are measured in the presence and absence of the compound. The compound's ability to enhance GABA-evoked currents is quantified. For mammalian cell assays, cells expressing recombinant GABAA receptors are loaded with calcium-sensitive dyes or membrane potential-sensitive dyes, and receptor activation is measured using plate readers.
|
| Animal Protocol |
CGS20625 has been studied in various in vivo animal models. The compound is typically administered orally or intraperitoneally. In anticonvulsant models, the compound is administered prior to seizure induction using pentylenetetrazol (PTZ) or maximal electroshock (MES), and the latency to seizure onset, seizure severity, and mortality are recorded. In anxiolytic models, behavioral tests such as the elevated plus maze, light-dark box, or conflict tests are used to assess anxiety-like behavior. Rotarod testing is used to assess motor coordination and sedation. The compound's oral bioavailability has been studied in dogs and humans, with improved absorption observed when administered in PEG 400 solution compared to powder formulations.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of CGS20625 have been characterized in preclinical and clinical studies. The compound is orally active and has been studied for oral absorption in dogs and humans. CGS20625 powder (20 mg) given orally exhibits slow, delayed absorption in both dogs and humans, with a Cmax of 0.26 ± 0.07 μg/mL at a Tmax of 3 hours in dogs, and 0.01 ± 0.004 μg/mL at 2 hours in humans. Administration in PEG 400 solution improves absorption, with a Cmax of 1.2 ± 0.10 μg/mL at a Tmax of 0.25 hours in dogs, and a Cmax of 0.10 ± 0.04 μg/mL at 0.5 hours in humans. The compound's highly water-insoluble nature presents challenges for oral bioavailability, requiring improved formulations.
|
| Toxicity/Toxicokinetics |
CGS20625 has been evaluated in preclinical toxicology studies. The compound's partial agonist profile at the benzodiazepine site is associated with a reduced side effect profile compared to full benzodiazepine agonists, with no sedation, muscle relaxation, or ethanol potentiation observed at anxiolytic doses. The compound has a wide therapeutic window, with rotarod impairment not observed at doses exceeding 300 times the anxiolytic dose. CGS20625 has been investigated in clinical studies for anxiety disorders. The compound is intended for research use only and is not approved for therapeutic applications.
|
| References |
1: Hirschberg Y, Oberle RL, Ortiz M, Lau H, Markowska M. Oral absorption of CGS-20625, an insoluble drug, in dogs and man. J Pharmacokinet Biopharm. 1995 Feb;23(1):11-23. doi: 10.1007/BF02353783. PMID: 8576841. 2: Williams M, Bennett DA, Loo PS, Braunwalder AF, Amrick CL, Wilson DE, Thompson TN, Schmutz M, Yokoyoma N, Wasley JW. CGS 20625, a novel pyrazolopyridine anxiolytic. J Pharmacol Exp Ther. 1989 Jan;248(1):89-96. PMID: 2563294. 3: Khom S, Baburin I, Timin EN, Hohaus A, Sieghart W, Hering S. Pharmacological properties of GABAA receptors containing gamma1 subunits. Mol Pharmacol. 2006 Feb;69(2):640-9. doi: 10.1124/mol.105.017236. Epub 2005 Nov 4. PMID: 16272224. 4: Jarvis MF, Bennett DA, Loo PA, Braunwalder AF, Thompson TN, Schmutz M, Yokoyoma N, Wasley JW, Williams M. CGS 20625, a novel pyrazolopyridine with selective anxiolytic activity. Prog Clin Biol Res. 1990;361:477-82. PMID: 1981266. 5: Tang AH, Franklin SR. The discriminative stimulus effects of diazepam in rats at two training doses. J Pharmacol Exp Ther. 1991 Sep;258(3):926-31. PMID: 1679851. 6: Brunner LA, Luders RC. Determination of a potential anxiolytic drug (CGS 20625) in human plasma by high-performance liquid chromatography. J Chromatogr. 1991 Aug 23;568(2):487-93. doi: 10.1016/0378-4347(91)80188-i. PMID: 1686029. 7: Bennett DA. Pharmacology of the pyrazolo-type compounds: agonist, antagonist and inverse agonist actions. Physiol Behav. 1987;41(3):241-5. doi: 10.1016/0031-9384(87)90360-x. PMID: 2893398. 8: Ogris W, Pöltl A, Hauer B, Ernst M, Oberto A, Wulff P, Höger H, Wisden W, Sieghart W. Affinity of various benzodiazepine site ligands in mice with a point mutation in the GABA(A) receptor gamma2 subunit. Biochem Pharmacol. 2004 Oct 15;68(8):1621-9. doi: 10.1016/j.bcp.2004.07.020. PMID: 15451405.
|
| Additional Infomation |
LSM-3520 belongs to the pyrazole class of compounds and cyclic compounds.
CGS20625 is a research-grade compound that has been studied as a non-benzodiazepine anxiolytic. The compound's partial agonist activity at the central benzodiazepine binding site of the GABAA receptor produces anxiolytic and anticonvulsant effects with a reduced side effect profile compared to classical benzodiazepines. CGS20625 has been investigated for the treatment of anxiety disorders and epilepsy. The compound's oral activity and favorable pharmacokinetic profile have supported its evaluation in clinical studies. CGS20625 serves as a valuable pharmacological tool for studying the dissociation between the therapeutic and adverse effects of benzodiazepine site ligands and for investigating the role of GABAA receptor subtypes in anxiety and epilepsy. |
| Molecular Formula |
C18H19N3O2
|
|---|---|
| Molecular Weight |
309.37
|
| Exact Mass |
309.148
|
| Elemental Analysis |
C, 69.88; H, 6.19; N, 13.58; O, 10.34
|
| CAS # |
111205-55-1
|
| PubChem CID |
163844
|
| Appearance |
Solid powder
|
| Density |
1.246g/cm3
|
| Boiling Point |
503.8ºC at 760mmHg
|
| Flash Point |
258.5ºC
|
| Vapour Pressure |
2.82E-10mmHg at 25°C
|
| Index of Refraction |
1.617
|
| LogP |
2.991
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
23
|
| Complexity |
436
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
COC1C=CC(N2NC3=C4CCCCCC4=NC=C3C2=O)=CC=1
|
| InChi Key |
XRUUVUYJUULCBQ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C18H19N3O2/c1-23-13-9-7-12(8-10-13)21-18(22)15-11-19-16-6-4-2-3-5-14(16)17(15)20-21/h7-11,19H,2-6H2,1H3
|
| Chemical Name |
Cyclohepta(b)pyrazolo(3,4-d)pyridin-3(2H)-one, 5,6,7,8,9,10-hexahydro-2-(4-methoxyphenyl)-
|
| Synonyms |
CGS20625; CGS-20625; CGS 20625;
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 3.2324 mL | 16.1619 mL | 32.3238 mL | |
| 5 mM | 0.6465 mL | 3.2324 mL | 6.4648 mL | |
| 10 mM | 0.3232 mL | 1.6162 mL | 3.2324 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
