MRS5698 is a selective Gi protein-coupled A3 adenosine receptor (A3AR) agonist with Ki of about 3 nM for human and mouse A3AR. MRS5698 may be utilized in pain and psoriasis research.

Physicochemical Properties

Molecular Formula	C28H23CLF2N6O3
Molecular Weight	564.98
Exact Mass	564.149
CAS #	1377273-00-1
PubChem CID	57523213
Appearance	Typically exists as solid at room temperature
LogP	3.262
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	7
Heavy Atom Count	40
Complexity	1030
Defined Atom Stereocenter Count	5
SMILES	ClC1=CC=CC(=C1)CNC1C2=C(N=C(C#CC3C=CC(=C(C=3)F)F)N=1)N(C=N2)[C@H]1[C@@H]([C@@H]([C@]2(C(NC)=O)C[C@@H]21)O)O
InChi Key	LYLLLJJYBWLGHW-CIZVZKTGSA-N
InChi Code	InChI=1S/C28H23ClF2N6O3/c1-32-27(40)28-11-17(28)22(23(38)24(28)39)37-13-34-21-25(33-12-15-3-2-4-16(29)9-15)35-20(36-26(21)37)8-6-14-5-7-18(30)19(31)10-14/h2-5,7,9-10,13,17,22-24,38-39H,11-12H2,1H3,(H,32,40)(H,33,35,36)/t17-,22-,23+,24+,28+/m1/s1
Chemical Name	(1S,2R,3S,4R,5S)-4-[6-[(3-chlorophenyl)methylamino]-2-[2-(3,4-difluorophenyl)ethynyl]purin-9-yl]-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide
Synonyms	MRS-5698; MRS 5698; MRS5698
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

ln Vitro	MRS5698 has greater selectivity and affinity (>3000-fold) as an agonist for A3R in humans and animals when compared to other adenosine receptors (ARs) [1]. In HEK-293T cells that express A3R continuously, MRS5698 (0.1–10 µM; 1 hour) elicits a substantial concentration-dependent A3R–mediated decrease in cAMP [3]. This effect is independent of light source.
ln Vivo	MRS5698 (3 nmol/day; intrathecal injection for 25 days) decreases NLRP3/IL-1β neuroinflammation caused by oxaliplatin and avoids hyperalgesia and mechanical allodynia brought on by the drug [2]. In C57BL/6N mice, MRS5698 (1 mg/kg; i.p. on days 2 and 3) decreased ear thickness induced by IL-23 (IL23 injection on days 0, 1, and 3) in the third and fourth experimental days [ 3].
Animal Protocol	Animal/Disease Models: Oxaliplatin-induced male Sprague Dawley rats (starting weight 200–250 g) [2] Doses: 3 nmol/day Route of Administration: Intrathecal injection for 25 days Experimental Results: Mechanical paw withdrawal threshold (in grams (unit) (PWT) increases rat. Attenuated oxaliplatin-induced NLRP3 expression and caspase 1 maturation in DH-SC. IL-1β levels are diminished in the spinal cord.
References	[1]. Efficient, large-scale synthesis and preclinical studies of MRS5698, a highly selective A3 adenosine receptor agonist that protects against chronic neuropathic pain. Purinergic Signal. 2015;11(3):371-387. [2]. Chemotherapy-induced pain is promoted by enhanced spinal adenosine kinase levels through astrocyte-dependent mechanisms. Pain. 2018;159(6):1025-1034. [3]. Optical control of adenosine A3 receptor function in psoriasis. Pharmacol Res. 2021 Aug;170:105731.

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	1.7700 mL	8.8499 mL	17.6997 mL
	5 mM	0.3540 mL	1.7700 mL	3.5399 mL
	10 mM	0.1770 mL	0.8850 mL	1.7700 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.