Drug Details

General Information of the Drug (ID: DR3243)
Name
Clofarabine
Synonyms
CAFdA; CFB; Clofarabina; Clofarabinum; Clofarex; Clolar; Evoltra; Clofarabine [USAN]; Clolar (TN); Evoltra (TN); Clofarabine (USAN/INN); Clolar, Evoltra, Clofarabine; Cl-F-Ara-A; (2R,3R,4S,5R)-5-(6-amino-2-chloropurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol; 2-Chloro-9-(2-deoxy-2-fluoro-b-D-arabinofuranosyl)-9H-purin-6-amine; 2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine; 2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine; 2-Cl-2'-F-araA; 2-chloro-9-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)adenine; 3S211048
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Molecular Type
Small molecule
Disease Myelodysplastic syndrome [ICD-11: 2A37] Approved [1]
Structure
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2D MOL

3D MOL

ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability
Clearance
The drug present in the plasma can be removed from the body at the rate of 7.7 mL/min/kg
Elimination
55% of drug is excreted from urine in the unchanged form
Half-life
The concentration or amount of drug in body reduced by one-half in 5.2 hours
Metabolism
The drug is metabolized via the deoxycytidine kinase and mono- and di-phosphokinases
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 4.234 micromolar/kg/day
Unbound Fraction
The unbound fraction of drug in plasma is 0.53%
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.75 L/kg
Water Solubility
The ability of drug to dissolve in water is measured as 1 mg/mL
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C10H11ClFN5O3
PubChem CID
119182
Canonical SMILES
C1=NC2=C(N=C(N=C2N1C3C(C(C(O3)CO)O)F)Cl)N
InChI
1S/C10H11ClFN5O3/c11-10-15-7(13)5-8(16-10)17(2-14-5)9-4(12)6(19)3(1-18)20-9/h2-4,6,9,18-19H,1H2,(H2,13,15,16)/t3-,4+,6-,9-/m1/s1
InChIKey
WDDPHFBMKLOVOX-AYQXTPAHSA-N
CAS Number
CAS 123318-82-1
TTD Drug ID
D0R5RR
DrugBank ID
DB00631
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Resveratrol      Gnetum parvifolium     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Down-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Down-regulation Expression MET  Molecule Info 
Pathway MAP
Down-regulation Expression PSG1  Molecule Info 
Pathway MAP
                    In-vitro Model MeT-5A CVCL_3749 Healthy Homo sapiens
MSTO-211H CVCL_1430 Pleural biphasic mesothelioma Homo sapiens
                    Experimental
                    Result(s)		 The synergistic antiproliferative effect of resveratrol and clofarabine is linked to the inhibition of Akt and Sp1 activities.
          Sulforaphane      Brassica oleracea     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CDKN2A  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Clofarabine in combination with sulforaphane significantly reactivates DNA methylation-silenced CDKN2A tumour suppressor and inhibits cancer cell growth at a non-invasive breast cancer stage.
Target and Pathway
Target(s) Bacterial Penicillin binding protein (Bact PBP)  Molecule Info  [4]
Ribonucleotide reductase (RIR)  Molecule Info  [4]
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6802).
Reference 2 Synergistic anti-cancer effects of resveratrol and chemotherapeutic agent clofarabine against human malignant mesothelioma MSTO-211H cells. Food Chem Toxicol. 2013 Feb;52:61-8.
Reference 3 Inhibition of breast cancer cell growth by the combination of clofarabine and sulforaphane involves epigenetically mediated CDKN2A upregulation. Nucleosides Nucleotides Nucleic Acids. 2018;37(5):280-289.
Reference 4 Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30.
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