Piclidenoson

Identification

Name
Piclidenoson
Accession Number
DB05511
Type
Small Molecule
Groups
Investigational
Description

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.

Structure
Thumb
Synonyms
Not Available
External IDs
CF-101 / CF101 / IB-MECA
Categories
UNII
30679UMI0N
CAS number
152918-18-8
Weight
Average: 510.2857
Monoisotopic: 510.051246546
Chemical Formula
C18H19IN6O4
InChI Key
HUJXGQILHAUCCV-MOROJQBDSA-N
InChI
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
IUPAC Name
(2S,3S,4R,5R)-3,4-dihydroxy-5-(6-{[(3-iodophenyl)methyl]amino}-9H-purin-9-yl)-N-methyloxolane-2-carboxamide
SMILES
CNC(=O)[[email protected]]1O[[email protected]]([[email protected]](O)[[email protected]@H]1O)N1C=NC2=C(NCC3=CC(I)=CC=C3)N=CN=C12

Pharmacology

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.

Structured Indications
Not Available
Pharmacodynamics

CF-101 is an adenoside A3 agonist for the treatment of a variety of autoimmune-inflammatory disorders, particularly rhematoid arthritis. In clinical trials, it was found to be safe, well tolerated and showed strong evidence of an anti-inflammatory effect in rheumatoid arthritis patients. In this trial, a statistically significant correlation was found between A(3)AR expression level and response to the drug, so A(3)AR expression may serve as a biopredictor of patient response.

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.

TargetActionsOrganism
UAdenosine receptor A3Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Bar-Yehuda S, Silverman MH, Kerns WD, Ochaion A, Cohen S, Fishman P: The anti-inflammatory effect of A3 adenosine receptor agonists: a novel targeted therapy for rheumatoid arthritis. Expert Opin Investig Drugs. 2007 Oct;16(10):1601-13. [PubMed:17922624]
External Links
PubChem Compound
123683
PubChem Substance
175427023
ChemSpider
110259
BindingDB
50118812
ChEBI
73286
ChEMBL
CHEMBL119709

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedPreventionRheumatoid Arthritis1
2CompletedTreatmentKeratoconjunctivitis Sicca1
2CompletedTreatmentPlaque Psoriasis1
2CompletedTreatmentRheumatoid Arthritis2
2Not Yet RecruitingTreatmentKnee Osteoarthritis (Knee OA)1
2Not Yet RecruitingTreatmentDiffuse posterior uveitis / Uveitis, Intermediate1
2RecruitingTreatmentGlaucoma / Ocular Hypertension1
2RecruitingTreatmentHepatocellular,Carcinoma1
2, 3CompletedTreatmentPlaque Psoriasis1
3CompletedTreatmentKeratoconjunctivitis Sicca1
3Not Yet RecruitingTreatmentRheumatoid Arthritis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.192 mg/mLALOGPS
logP1ALOGPS
logP0.6ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)12.39ChemAxon
pKa (Strongest Basic)4.84ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area134.42 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity113.25 m3·mol-1ChemAxon
Polarizability45.06 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8965
Blood Brain Barrier-0.5807
Caco-2 permeable-0.6658
P-glycoprotein substrateSubstrate0.5339
P-glycoprotein inhibitor INon-inhibitor0.8687
P-glycoprotein inhibitor IIInhibitor0.5846
Renal organic cation transporterNon-inhibitor0.9108
CYP450 2C9 substrateNon-substrate0.7615
CYP450 2D6 substrateNon-substrate0.835
CYP450 3A4 substrateSubstrate0.5348
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9072
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7671
Ames testNon AMES toxic0.7609
CarcinogenicityNon-carcinogens0.8473
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6008 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9801
hERG inhibition (predictor II)Non-inhibitor0.5685
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0uxr-2489100000-ca8ba69b00dc87548630

Taxonomy

Description
This compound belongs to the class of organic compounds known as purine nucleosides. These are compounds comprising a purine base attached to a ribosyl or deoxyribosyl moiety.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Purine nucleosides
Sub Class
Not Available
Direct Parent
Purine nucleosides
Alternative Parents
6-alkylaminopurines / Glycosylamines / Benzylamines / Secondary alkylarylamines / Aminopyrimidines and derivatives / Iodobenzenes / Aryl iodides / Imidolactams / N-substituted imidazoles / Tetrahydrofurans
show 10 more
Substituents
Purine nucleoside / N-glycosyl compound / 6-alkylaminopurine / Glycosyl compound / 6-aminopurine / Imidazopyrimidine / Purine / Benzylamine / Halobenzene / Iodobenzene
show 34 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organoiodine compound, monocarboxylic acid amide, adenosines (CHEBI:73286)

Targets

Details
1. Adenosine receptor A3
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
G-protein coupled adenosine receptor activity
Specific Function
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. Possible role in reproduction.
Gene Name
ADORA3
Uniprot ID
P0DMS8
Uniprot Name
Adenosine receptor A3
Molecular Weight
36184.175 Da

Drug created on November 18, 2007 11:25 / Updated on December 01, 2017 15:36