CAS 123318-82-1|2-CHLORO-9-(2-DEOXY-2-FLUORO-B -D-ARABINOFURANOSYL)-9H-PURIN-6-AMINE|clofarabine|(2R,3R,4S,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol|clofarabine|Ev...

General Information

Structure

Molecular Formula

C₁₀H₁₁ClFN₅O₃

Molecular Mass

303.6774432

Exact Mass

303.05344514

Charge

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

Canonic Smiles

OC[C@H]1O[C@H]([C@H]([C@@H]1O)F)n1cnc2c1nc(Cl)nc2N

Isomeric Smiles

Clc1nc2n([C@@H]3O[C@@H]([C@@H](O)[C@@H]3F)CO)cnc2c(n1)N

Calculated Properties

JChem

Acid pKa

12.70945

H Acceptors

H Donor

LogD (pH = 5.5)

-0.2913289

LogD (pH = 7.4)

-0.29132396

Log P

-0.29132175

Molar Refractivity

67.0021

Polarizability

25.781265

Polar Surface Area

119.31

Rotatable Bonds

Lipinski's Rule of Five

true

ALOGPS 2.1

Log P

0.32

LOG S

-1.79

Solubility (Water)

4.89e+00 g/l

Data Source

Names and Identifiers

Synonyms

2-CHLORO-9-(2-DEOXY-2-FLUORO-B -D-ARABINOFURANOSYL)-9H-PURIN-6-AMINEclofarabineClofarabineClolarEvoltra(2R,3R,4S,5R)-5-(6-amino-2-chloropurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol, 2-chloro-2′-arabino-fluoro-2′-deoxyadenosineClofarabine

IUPAC Traditional name

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

IUPAC name

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

Brand Name

EvoltraClolar

Names and Identifiers

Registration numbers

PubChem SID

CAS Number

PubChem CID

MDL Number

Registration numbers

Properties

Physical Property

Hydrophobicity(logP)

Solubility

DMSO

DMSO: >10 mg/mL

Apperance

white powder

Pharmacology Properties

Target

DNA/RNA synthesis

Mechanism of Action

Purine nucleoside antimetabolite

Product Information

Salt Data

Free Base

Empirical Formula (Hill Notation)

C10H11ClFN5O3

Purity

≥98% (HPLC)

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)

Description

2 Isomers

Properties

Related Proteins

No Data Available

Click here to submit data

Molecular Spectra

No Data Available

Click here to submit data

Molecule Details

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/m² basis) has been 70 mg/m²/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]

DB07554

Drug information: experimental

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.

Molecule Details

References

PubChem Literature

From Data Sources

• 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

• Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. 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

• Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. Pubmed

• http://en.wikipedia.org/wiki/Clofarabine

References

Bioactivity

PubChem BioAssay

Bioactivity

Names and Identifiers

Synonyms

IUPAC Traditional name

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

IUPAC name

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

Brand Name

EvoltraClolar

Registration numbers

PubChem SID

CAS Number

PubChem CID

MDL Number

Molecule Details

DB00631

Drug Groups

approved; investigational

Description

Indication

Pharmacology

Toxicity

Affected Organisms

Humans and other mammals

Biotransformation

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]

• 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]

DB07554

Drug information: experimental

Selleck Chemicals

S1218

Sigma Aldrich

C7495

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

References

PubChem Literature

From Data Sources

• 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

• Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. 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

• Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. Pubmed

• http://en.wikipedia.org/wiki/Clofarabine

Bioactivity

PubChem BioAssay

Properties

Physical Property

Hydrophobicity(logP)

Solubility

DMSO

DMSO: >10 mg/mL

Apperance

white powder

Pharmacology Properties

Target

DNA/RNA synthesis

Mechanism of Action

Purine nucleoside antimetabolite

Product Information

Salt Data

Free Base

Empirical Formula (Hill Notation)

C10H11ClFN5O3

Purity

≥98% (HPLC)

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)

Description

2 Isomers

Molecule

ID:513