Namodenoson (2-Cl-IB-MECA; CF102; CF-102) is a novel, potent, orally bioavailable, and highly selective adenosine A3 receptor (A3AR) agonist with potential anticancer activity. The agonist of the adenosine A3 receptor CF102 specifically binds to and activates the A3AR expressed on the cell surface. This deregulation of Wnt and NF-kB signal transduction pathways may lead to the apoptosis of tumor cells that express A3AR. Hepatocellular carcinoma (HCC) cells are among the solid tumor cell types that have high expression levels of A3AR, a G protein-coupled receptor that is crucial to cellular proliferation.

Physicochemical Properties

Molecular Formula	C18H18CLIN6O4
Molecular Weight	544.7308
Exact Mass	544.012
Elemental Analysis	C, 39.69; H, 3.33; Cl, 6.51; I, 23.30; N, 15.43; O, 11.75
CAS #	163042-96-4
PubChem CID	3035850
Appearance	Solid powder
Density	2.0±0.1 g/cm3
Melting Point	209 °C
Index of Refraction	1.814
LogP	3.14
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	5
Heavy Atom Count	30
Complexity	623
Defined Atom Stereocenter Count	4
SMILES	IC1=C([H])C([H])=C([H])C(=C1[H])C([H])([H])N([H])C1=C2C(=NC(=N1)Cl)N(C([H])=N2)[C@@]1([H])[C@@]([H])([C@@]([H])([C@@]([H])(C(N([H])C([H])([H])[H])=O)O1)O[H])O[H]
InChi Key	IPSYPUKKXMNCNQ-PFHKOEEOSA-N
InChi Code	InChI=1S/C18H18ClIN6O4/c1-21-16(29)13-11(27)12(28)17(30-13)26-7-23-10-14(24-18(19)25-15(10)26)22-6-8-3-2-4-9(20)5-8/h2-5,7,11-13,17,27-28H,6H2,1H3,(H,21,29)(H,22,24,25)/t11-,12+,13-,17+/m0/s1
Chemical Name	(2S,3S,4R,5R)-5-[2-chloro-6-[(3-iodophenyl)methylamino]purin-9-yl]-3,4-dihydroxy-N-methyloxolane-2-carboxamide
Synonyms	CF102; Cl-IB-MECA; CF-102; 2-Cl-IB-MECA; CF 102; Namodenoson; Chloro-IB-MECA
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	A3 adenosine receptor ( Ki = 0.33 nM )
ln Vitro	Namodenoson (2-Cl-IB-MECA) 100 nM significantly reorganized the cytoskeleton in human ADF cells of the astroglial lineage, resulting in the appearance of stress fibers and multiple cell protrusions. High Namodenoson (2-Cl-IB-MECA) concentrations directly result in a Ca2+ influx[2].
ln Vivo	After receiving 200 μg/kg of Namodenoson (2-Cl-IB-MECA) intravenously, there was a brief drop in blood pressure and a 50–100 fold increase in plasma histamine levels. Hemodynamic effects were absent when Namodenoson (2-Cl-IB-MECA) was administered in two doses[1].
Cell Assay	The indicated drug concentrations were applied to the cells for a duration of 48 hours.
References	[1]. Hemodynamic effects and histamine release elicited by the selective adenosine A3 receptor agonist 2-Cl-IB-MECA in conscious rats. Eur J Pharmacol. 1996 Jul 25;308(3):311-4. [2]. Adenosine A3 receptors: novel ligands and paradoxical effects. Trends Pharmacol Sci. 1998 May;19(5):184-91.
Additional Infomation	Namodenoson has been used in trials studying the treatment of Chronic Hepatitis C and Hepatocellular Carcinoma. Namodenoson is an orally bioavailable, synthetic, highly selective adenosine A3 receptor (A3AR) agonist with potential antineoplastic activity. Namodenoson selectively binds to and activates the cell surface-expressed A3AR, deregulating Wnt and NF-kB signal transduction pathways downstream, which may result in apoptosis of A3AR-expressing tumor cells. A3AR, a G protein-coupled receptor, is highly expressed on the cell surfaces of various solid tumor cell types, including hepatocellular carcinoma (HCC) cells, and plays an important role in cellular proliferation.

Solubility Data

Solubility (In Vitro)

DMSO: ~100 mg/mL (~183.6 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.82 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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: 2.08 mg/mL (3.82 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (3.82 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8358 mL	9.1789 mL	18.3577 mL
	5 mM	0.3672 mL	1.8358 mL	3.6715 mL
	10 mM	0.1836 mL	0.9179 mL	1.8358 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.