PSB 0777 ammonium is a potent and specific adenosine A2A receptor agonist/activator with Kis of 44.4 nM and 360 nM for rat and human A2A receptors respectively. The Kis of PSB 0777 ammonium on rat and human A1 receptors are ≥10000 nM and 541 nM respectively. PSB 0777 ammonium displays poor brain penetration and oral bioavailability (F). PSB 0777 ammonium may be utilized in inflammatory bowel disease (IBS) research.

Physicochemical Properties

Molecular Formula	C18H24N6O7S2
Molecular Weight	500.55
Exact Mass	500.114
CAS #	2122196-16-9
Related CAS #	PSB 0777 ammonium hydrate
PubChem CID	90488932
Appearance	Typically exists as solid at room temperature
Hydrogen Bond Donor Count	6
Hydrogen Bond Acceptor Count	13
Rotatable Bond Count	7
Heavy Atom Count	33
Complexity	736
Defined Atom Stereocenter Count	4
SMILES	C1=CC(=CC=C1CCSC2=NC(=C3C(=N2)N(C=N3)[C@H]4[C@H]([C@@H]([C@H](O4)CO)O)O)N)S(=O)(=O)O.N
InChi Key	AYQGFWKUGKSGCZ-VSAOVUCUSA-N
InChi Code	InChI=1S/C18H21N5O7S2.H3N/c19-15-12-16(23(8-20-12)17-14(26)13(25)11(7-24)30-17)22-18(21-15)31-6-5-9-1-3-10(4-2-9)32(27,28)29;/h1-4,8,11,13-14,17,24-26H,5-7H2,(H2,19,21,22)(H,27,28,29);1H3/t11-,13-,14+,17-;/m1./s1
Chemical Name	4-[2-[6-amino-9-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]sulfanylethyl]benzenesulfonic acid;azane
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)

Biological Activity

Targets	Ki: 44.4 nM (rat A2A), 360 nM (human A2A), ≥10000 nM (rat A1) and 541 nM (human A1)[1]
ln Vitro	Compound 7, or PSB 0777 ammonium, exhibits significant selectivity (>225-fold) for the A2AAR relative to the other AR subtypes (Ki values of ≫10000 for the human A3 receptor and >10000 nM for the human A2B receptor, respectively). In CHO-K1 cells, PSB 0777 ammonium exhibits full agonistic activity at A2AAR, with an EC50 value of 117 nM[1]. Human β1 (Ki=4.4 μM) and β3 (Ki=3.3 μM) adrenergic receptors are bound by PSB-0777 ammonium[2]. Acetylcholine (Ach, 1 mM) contractions in untreated and inflamed rat ileum/jejunum preparations are concentration-dependently increased by ammonium (0.1 µM, 1 µM, 10 µM)[1].
ln Vivo	Ammonium PSB 0777 (0.4 mg/kg/day; oral gavage; day 5 to day 10) significantly reduces the infiltration of inflammatory cells and improves the architecture of the colonic mucosa[3]. In C57BL/6J mice, PSB 0777 ammonium (0.03, 0.3, and 3 mg /kg; ip) induces dose-dependent hypothermia and hypoactivity[2]. When taken orally, PSB 0777 ammonium cannot be absorbed by the digestive mucosa in a systematic manner. Rats with PSB 0777 ammonium (0.4 mg/kg/day; PO) showed very low plasma concentrations at 30 min (below 5 nM) and no plasma concentrations at 60 min. Plasma concentrations are clearly visible at 30 minutes, start to decline at 60 minutes, and become undetectable at 120 and 240 minutes when PSB 0777 ammonium (0.4 mg/kg/day; IP) is added[3].
Animal Protocol	Animal/Disease Models: Albino male SD (Sprague-Dawley) rats of 200 g with Oxazolone-induced colitis[3] Doses: 0.4 mg/kg Route of Administration: Oral gavage; daily; from the day 5 to 10 Experimental Results: Caused a marked reduction of inflammatory cell infiltration and an amelioration of colonic mucosal architecture alone or in combination with Dexamethasone (1 mg/kg/day). Counteracted Dramatically the increment of colonic myeloperoxidase ( MPO) levels associated with colitis.
References	[1]. Ali El-Tayeb, et al. Development of Polar Adenosine A2A Receptor Agonists for Inflammatory Bowel Disease: Synergism with A2B Antagonists. ACS Med Chem Lett. 2011 Oct 10;2(12):890-5. [2]. Jesse Lea Carlin, et al.Activation of adenosine A 2A or A 2B receptors causes hypothermia in mice. Neuropharmacology. 2018 Sep 1;139:268-278. [3]. L Antonioli, et al. Anti-inflammatory effect of a novel locally acting A 2A receptor agonist in a rat model of oxazolone-induced colitis. Purinergic Signal. 2018 Mar;14(1):27-36.

Solubility Data

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.9978 mL	9.9890 mL	19.9780 mL
	5 mM	0.3996 mL	1.9978 mL	3.9956 mL
	10 mM	0.1998 mL	0.9989 mL	1.9978 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.