(2R,3R,4S,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol

• ChemBase ID: 513
• Molecular Formular: C10H11ClFN5O3
• Molecular Mass: 303.6774432
• Monoisotopic Mass: 303.05344514
• SMILES: Clc1nc2n([C@@H]3O[C@@H]([C@@H](O)[C@@H]3F)CO)cnc2c(n1)N
• Canonical SMILES: OC[C@H]1O[C@H]([C@H]([C@@H]1O)F)n1cnc2c1nc(Cl)nc2N
• InChI: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: (2R,3R,4S,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol
• IUPAC Traditional name: clofarabine; (2R,3R,4S,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol
• Brand Name: Clolar; Evoltra
• Synonyms: clofarabine; Clofarabine; 2-CHLORO-9-(2-DEOXY-2-FLUORO-B -D-ARABINOFURANOSYL)-9H-PURIN-6-AMINE; (2R,3R,4S,5R)-5-(6-amino-2-chloropurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol, 2-chloro-2′-arabino-fluoro-2′-deoxyadenosine; Clofarabine; Clolar; Evoltra

Database IDs

• CAS Number: 123318-82-1
• MDL Number: MFCD00871077
• PubChem SID: 160963976; 46504968
• PubChem CID: 119182

CALCULATED PROPERTIES

JChem

• Acid pKa: 12.70945
• H Acceptors: 7
• H Donor: 3
• LogD (pH = 5.5): -0.2913289
• LogD (pH = 7.4): -0.29132396
• Log P: -0.29132175
• Molar Refractivity: 67.0021 cm^3
• Polarizability: 25.781265 Å^3
• Polar Surface Area: 119.31 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 0.32
• LOG S: -1.79
• Solubility (Water): 4.89e+00 g/l

PROPERTIES

Physical Property

• Solubility: DMSO; DMSO: >10 mg/mL
• Apperance: white powder
• Hydrophobicity(logP): 0

Safety Information

• Storage Condition: -20°C
• RTECS: UD7473000
• European Hazard Symbols: Toxic (T)
• UN Number: 2811
• German water hazard class: 2
• Hazard Class: 6.1
• Packing Group: 3
• Risk Statements: 25
• Safety Statements: 45
• GHS Pictograms: GHS06
• GHS Signal Word: Danger
• GHS Hazard statements: H300
• GHS Precautionary statements: P264-P301 + P310
• Personal Protective Equipment: Eyeshields, Faceshields, Gloves, type P2 (EN 143) respirator cartridges
• RID/ADR: UN 2811 6.1/PG 3
• Storage Temperature: 2-8°C

Pharmacology Properties

• Target: DNA/RNA synthesis
• Mechanism of Action: Purine nucleoside antimetabolite

Product Information

• Purity: ≥98% (HPLC)
• Salt Data: Free Base
• Description: 2 Isomers
• Application(s): Used in paediatrics to treat a type of leukaemia called relapsed or refractory acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML) and juvenile myelomonocytic leukaemia (JMML)
• Empirical Formula (Hill Notation): C10H11ClFN5O3

DETAILS

DrugBank - DB07554

Drug information: experimental

DrugBank - DB00631

• Drug Groups: approved; investigational
• Description: Clofarabine is a purine nucleoside antimetabolite that is being studied in the treatment of cancer. It is marketed in the U.S. and Canada as Clolar. In Europe and Australia/New Zealand the product is marketed under the name Evoltra.; ; Clofarabine is used in paediatrics to treat a type of leukaemia called relapsed or refractory acute lymphoblastic leukaemia (ALL), only after at least two other types of treatment have failed. It is not known if the drug extends life expectancy. Some investigations of effectiveness in cases of acute myeloid leukaemia (AML) and juvenile myelomonocytic leukaemia (JMML) have been carried out.
• Indication: For the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphocytic (lymphoblastic) leukemia after at least two prior regimens. It is designated as an orphan drug by the FDA for this use.
• Pharmacology: Clofarabine is a purine nucleoside antimetabolite that differs from other puring nucleoside analogs by the presence of a chlorine in the purine ring and a flourine in the ribose moiety. Clofarabine seems to interfere with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by clofarabine, other effects also occur. Clofarabine prevents cells from making DNA and RNA by interfering with the synthesis of nucleic acids, thus stopping the growth of cancer cells.
• Toxicity: There were no known overdoses of clofarabine. The highest daily dose administered to a human to date (on a mg/m^2 basis) has been 70 mg/m^2/day × 5 days (2 pediatric ALL patients). The toxicities included in these 2 patients included grade 4 hyperbilirubinemia, grade 2 and 3 vomiting, and grade 3 maculopapular rash.
• Affected Organisms: Humans and other mammals
• Biotransformation: Clofarabine is sequentially metabolized intracellularly to the 5’-monophosphate metabolite by deoxycytidine kinase and mono- and di-phosphokinases to the active 5’-triphosphate metabolite. Clofarabine has high affinity for the activating phosphorylating enzyme, deoxycytidine kinase, equal to or greater than that of the natural substrate, deoxycytidine.
• Half Life: The terminal half-life is estimated to be 5.2 hours.
• Protein Binding: 47% bound to plasma proteins, predominantly to albumin.
• Elimination: Based on 24-hour urine collections in the pediatric studies, 49 - 60% of the dose is excreted in the urine unchanged.
• Distribution: * 172 L/m2
• Clearance: * 28.8 L/h/m2 [Pediatric patients (2 - 19 years old) with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) receiving 52 mg/m2 dose]
• References: Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. [Pubmed] ; Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. [Pubmed] ; Lech-Maranda E, Korycka A, Robak T: Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity. Mini Rev Med Chem. 2009 Jun;9(7):805-12. [Pubmed] ; Larson ML, Venugopal P: Clofarabine: a new treatment option for patients with acute myeloid leukemia. Expert Opin Pharmacother. 2009 Jun;10(8):1353-7. [Pubmed] ; Zhenchuk A, Lotfi K, Juliusson G, Albertioni F: Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009 Dec 1;78(11):1351-9. Epub 2009 Jul 1. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1218

Research Area: Non-Hodgkin's lymphoma,B-cell lymphoma
Biological Activity:
Clofarabine is a second generation purine nucleoside analog with antineoplastic activity. It is phosphorylated intracellularly, which inhibits the enzymatic activities of ribonucleotide reductase (IC50 = 65 nM) and DNA polymerase, resulting in inhibition of DNA repair and synthesis of DNA and RNA. This nucleoside analog also disrupts mitochondrial function and membrane integrity, resulting in the release of pre-apoptotic factors, including cytochrome C and apoptotic-inducing factor, which activate apoptosis. [1]It is used for treating relapsed or refractory acute lymphoblastic leukaemia (ALL) in children, after at least two other types of treatment have failed. [2]

Sigma Aldrich - C7495

Biochem/physiol Actions
Clofarabine is a purine nucleoside antimetabolite. Clofarabine is toxic to nondividing lymphocytes and monocytes.

REFERENCES

• Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. Pubmed
• Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. Pubmed
• Lech-Maranda E, Korycka A, Robak T: Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity. Mini Rev Med Chem. 2009 Jun;9(7):805-12. Pubmed
• Larson ML, Venugopal P: Clofarabine: a new treatment option for patients with acute myeloid leukemia. Expert Opin Pharmacother. 2009 Jun;10(8):1353-7. Pubmed
• Zhenchuk A, Lotfi K, Juliusson G, Albertioni F: Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009 Dec 1;78(11):1351-9. Epub 2009 Jul 1. Pubmed
• http://en.wikipedia.org/wiki/Clofarabine