| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Adenosine A2A receptor ( Ki = 27 nM )
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|---|---|
| ln Vitro |
CGS21680 markedly increased the expression of CD39 and CD73. Adenosine triphosphate (ATP) hydrolysis and adenosine synthesis are accelerated by CGS21680 [1]. While CGS21680 (10 nM) by itself demonstrated very little survival activity, the addition of the phosphodiesterase inhibitor IBMX greatly increased this activity. Neurotrophin receptor transactivation and the adenylyl cyclase-cAMP-PKA pathway work together to provide CGS21680's survival effect on cultured motor neurons [4].
|
| ln Vivo |
The intervention CGS21680 (1 mg/kg/ip) encourages the growth of EAN. In Lewis rats, CGS21680 aggravates experimental autoimmune neuritis brought on by bovine peripheral myelin. A drop in CD4+ Foxp3+ T cells and an increase in CD4+ CXCR5+ T cells, B cells, dendritic cells, and antigen-specific autoantibodies are observed in conjunction with the worsening of the disease; the latter may be brought on by CGS21680-induced IL-2 suppression [2]. Rats treated with CGS21680 (0.1 mg/kg, i.p.) saw a brief rise in heart rate but no change in blood pressure; at 0.01 mg/kg, neither the heart rate nor blood pressure changed. Both dosages of CGS21680 prevented cerebral impairments from the first day to seven days following acute MCAo. During this period, it enhanced the cellularity of the ischemic cortex and striatum, decreased microgliosis and astrogliosis, and improved myelin structure in the striatum. CGS21680 decreased the amount of granulocytes infiltrating into ischemic tissue two days following transient MCAo [3].
|
| Enzyme Assay |
Cloning of the human adenosine receptors, stable transfection of cells, cell culture, membrane preparation, radioligand binding, and adenylyl cyclase activity have been fully described elsewhere. Briefly, all human subtypes were stably transfected into Chinese hamster ovary (CHO) cells in order to be able to study their pharmacological profile in an identical cellular background utilizing radioligand binding studies (A1, A2A, A3) or adenylyl cyclase activity assays (A2B). Receptor binding affinity was determined using [3 H]CCPA as radioligand at A1 receptors, whereas [3 H]NECA was used at A2A and A3 subtypes. The procedure was performed as described previously. Due to the lack of a suitable radioligand the relative potency of agonists at A2B adenosine receptors was determined in adenylyl cyclase experiments. The procedure was carried out as described previously with minor modifications[2].
|
| Cell Assay |
The survival activity of adenosine A(2A) agonist CGS21680 on motoneurons in culture through the transactivation of neurotrophin receptor TrkB has been reported previously; however, since adenosine A(2A) receptor belongs to a Gs-protein-coupled receptor, we investigated the involvement of the cAMP pathway in the survival activity of CGS21680 using purified motoneurons in culture. CGS21680 alone showed only small survival activity, but the activity was significantly enhanced by the addition of a phosphodiesterase inhibitor, IBMX. This survival activity was partially inhibited by a protein kinase A inhibitor H89 or a neurotrophin receptor tyrosine kinase inhibitor K252a, and was completely inhibited by their combination. These results indicate that the survival activity of CGS21680 on motoneurons is exerted by the mixed effect of the adenylate cyclase-cAMP-PKA pathway and transactivation of Trk neurotrophin receptor. Under conditions in which the maximum survival of motoneurons was supported by sufficient concentrations of brain-derived neurotrophic factor (BDNF), a TrkB ligand, the addition of 100μM AMPA for 3 days led to significant cell death. Treatment with CGS21680 and IBMX protected motoneurons from the toxicity of AMPA, further supporting the presence of a TrkB-independent pathway of CGS21680 activity and suggesting a novel therapeutic approach to motoneuron diseases such as amyotrophic lateral sclerosis[5].
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| References |
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| Additional Infomation |
CGS-21680 is a derivative of adenosine, in which the 5'-hydroxymethyl group is replaced by an N-ethylcarboxamide group, and the hydrogen at the 2-position of adenine is replaced by a 4-(2-carboxyethyl)phenylethylamino group. It is an adenosine A2A receptor agonist and anti-inflammatory agent. It belongs to the adenosine class of compounds and is a monocarboxylic acid and dicarboxylic acid monoamide. Its function is related to adenosine.
|
| Molecular Formula |
C23H29N7O6
|
|---|---|
| Molecular Weight |
499.5197
|
| Exact Mass |
499.217931
|
| CAS # |
120225-54-9
|
| Related CAS # |
CGS 21680 Hydrochloride;124431-80-7
|
| PubChem CID |
3086599
|
| Appearance |
White to off-white solid
|
| LogP |
0.88
|
| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
11
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
36
|
| Complexity |
755
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
O1[C@]([H])(C(N([H])C([H])([H])C([H])([H])[H])=O)[C@]([H])([C@]([H])([C@]1([H])N1C([H])=NC2=C(N([H])[H])N=C(N([H])C([H])([H])C([H])([H])C3C([H])=C([H])C(=C([H])C=3[H])C([H])([H])C([H])([H])C(=O)O[H])N=C12)O[H])O[H]
|
| InChi Key |
PAOANWZGLPPROA-RQXXJAGISA-N
|
| InChi Code |
InChI=1S/C23H29N7O6/c1-2-25-21(35)18-16(33)17(34)22(36-18)30-11-27-15-19(24)28-23(29-20(15)30)26-10-9-13-5-3-12(4-6-13)7-8-14(31)32/h3-6,11,16-18,22,33-34H,2,7-10H2,1H3,(H,25,35)(H,31,32)(H3,24,26,28,29)/t16-,17+,18-,22+/m0/s1
|
| Chemical Name |
3-[4-[2-[[6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxyoxolan-2-yl]purin-2-yl]amino]ethyl]phenyl]propanoic acid
|
| Synonyms |
CGS-21680; 2-(4-(2-Carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; 124182-57-6; CGS21680; 3-[4-[2-[[6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxyoxolan-2-yl]purin-2-yl]amino]ethyl]phenyl]propanoic acid; CHEMBL331372;
|
| 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 (~100.1 mM; with ultrasonication)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.00 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (5.00 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0019 mL | 10.0096 mL | 20.0192 mL | |
| 5 mM | 0.4004 mL | 2.0019 mL | 4.0038 mL | |
| 10 mM | 0.2002 mL | 1.0010 mL | 2.0019 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.
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