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Piclidenoson, formerly known as CF101, is a specific agonist to the A3 adenosine receptor, which inhibits the development of colon carcinoma growth in cell cultures and xenograft murine models. It has been demonstrated that CF101 suppresses the expression of the PKB/Akt and NF-κB proteins. Drug resistance is avoided by CF101, which increases the cytotoxic effect of 5-FU. The development of CF101 as a 5-FU adjunct treatment is suggested by its myeloprotective effect.
Physicochemical Properties
| Molecular Formula | C18H19IN6O4 |
| Molecular Weight | 510.28 |
| Exact Mass | 510.051 |
| Elemental Analysis | C, 42.37; H, 3.75; I, 24.87; N, 16.47; O, 12.54 |
| CAS # | 152918-18-8 |
| Related CAS # | 152918-18-8 |
| PubChem CID | 123683 |
| Appearance | White to off-white solid powder |
| Density | 2.0±0.1 g/cm3 |
| Index of Refraction | 1.808 |
| LogP | 2.08 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 29 |
| Complexity | 589 |
| Defined Atom Stereocenter Count | 4 |
| SMILES | IC1=C([H])C([H])=C([H])C(=C1[H])C([H])([H])N([H])C1=C2C(=NC([H])=N1)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 | HUJXGQILHAUCCV-MOROJQBDSA-N |
| InChi Code | InChI=1S/C18H19IN6O4/c1-20-17(28)14-12(26)13(27)18(29-14)25-8-24-11-15(22-7-23-16(11)25)21-6-9-3-2-4-10(19)5-9/h2-5,7-8,12-14,18,26-27H,6H2,1H3,(H,20,28)(H,21,22,23)/t12-,13+,14-,18+/m0/s1 |
| Chemical Name | (2S,3S,4R,5R)-3,4-dihydroxy-5-(6-(3-iodobenzylamino)-9H-purin-9-yl)-N-methyltetrahydrofuran-2-carboxamide |
| Synonyms | ALB-7208; ALB 7208; CF101; CF-101; CF 101; ALB7208; IB MECA; Piclidenoson |
| 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 | A3AR |
| ln Vitro |
Piclidenoson can reduce the amount of cAMP stimulated by forskolin, with EC50 values in OVCAR-3 cells of 0.82 μM and in Caov-4 cells of 1.2 μM, respectively [2]. Piclidenoson (0.0001-100 μM; 48 hours) dramatically lowers human ovarian line cell viability in a dose-dependent manner; for OVCAR-3 and Caov-4 cells, the IC50s are 32.14 μM and 45.37 μM, respectively [2]. Piclidenoson (0.001-100 μM; 48 hours) through the caspase pathway. |
| ln Vivo | Piclidenoson (105 μg/kg; IP) improvement γ The survival rate of irradiated mice [3]. |
| Cell Assay |
Cell Line: OVCAR-3 cells, Caov-4 cells Concentration: 0.0001-100 μM Incubation Time: 48 hours Result: Resulted in a dose-dependent reduction in the cell viability. |
| Animal Protocol |
B10CBAF1 male mice aged 3 months (average 30 g) 105 μg/kg Intraperitoneal injection, 0.5 h after irradiation |
| References |
[1]. Activation of Phosphoinositide Breakdown and Elevation of Intracellular Calcium in a Rat RBL-2H3 Mast Cell Line by Adenosine Analogs: Involvement of A(3)-Adenosine Receptors? Drug Dev Res. 1996 Sep 1;39(1):36-46. [2]. Mitochondrial and caspase pathways are involved in the induction of apoptosis by IB-MECA in ovarian cancer cell lines. Tumour Biol. 2014 Nov;35(11):11027-11039. [3]. Agonist of the adenosine A3 receptor, IB-MECA, and inhibitor of cyclooxygenase-2, meloxicam, given alone or in a combination early after total body irradiation enhance survival of γ-irradiated mice. Radiat Environ Biophys. 2014 Mar;53(1):211-215. [4]. Potential Therapeutic Options for COVID-19: Current Status, Challenges, and Future Perspectives. Front Pharmacol. 2020; 11: 572870. |
| Additional Infomation |
3-iodobenzyl-5'-N-methylcarboxamidoadenosine is a derivative of adenosine in which the 5'-hydroxymethyl group is replaced by N-ethylcarboxamido and one of the hydrogens of the exocyclic amino function is substituted by a 3-iodobenzyl group. It has a role as an adenosine A3 receptor agonist. It is a member of adenosines, an organoiodine compound and a monocarboxylic acid amide. It is functionally related to an adenosine. CF 101 (known generically as IB-MECA) is an anti-inflammatory drug for rheumatoid arthritis patients. Its novel mechanism of action relies on antagonism of adenoside A3 receptors. CF101 is supplied as an oral drug and has an excellent safety profile. It is also being considered for the treatment of other autoimmune-inflammatory disorders, such as Crohn's disease, psorasis and dry eye syndrome. Piclidenoson is an orally bioavailable, adenosine A3 receptor (A3AR) agonist with potential anti-inflammatory activity. Upon administration, piclidenoson selectively targets, binds to and activates the cell surface-expressed A3AR, thereby activating transduction pathways in which A3AR plays a key role. This inhibits nuclear factor-kappa B (NF-kB) signaling and inhibits inflammatory cytokine production, such as tumor necrosis factor (TNF) and several interleukins. A3AR, a G protein-coupled receptor, plays a key role in many inflammatory diseases, and in certain types of cancer. Drug Indication Investigated for use/treatment in cancer/tumors (unspecified), eye disorders/infections, psoriasis and psoriatic disorders, and rheumatoid arthritis. Can-Fite BioPharma has reported that by targeting the adenosine A3-receptor, CF101 may also be used to treat Crohn's disease, a serious gastrointestinal disorder. Mechanism of Action CF 101 is an A(3)AR agonist. A(3)AR is highly expressed in inflammatory cells and overexpressed in peripheral blood mononuclear cells, reflecting its role in the remote inflammatory process. In normal tissues, there is low adenoside A3 receptor expression. A(3)AR activation with a specific agonist deregulates the NF-kappaB signaling pathway in inflammatory cells and initiates immunomodulatory effects. |
Solubility Data
| Solubility (In Vitro) | DMSO: ≥ 45 mg/mL (~88.2 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.90 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 25.0 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: ≥ 2.5 mg/mL (4.90 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 25.0 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: ≥ 2.5 mg/mL (4.90 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 25.0 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 | 1.9597 mL | 9.7985 mL | 19.5971 mL | |
| 5 mM | 0.3919 mL | 1.9597 mL | 3.9194 mL | |
| 10 mM | 0.1960 mL | 0.9799 mL | 1.9597 mL |