U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C10H11ClFN5O3
Molecular Weight 303.677
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CLOFARABINE

SMILES

NC1=NC(Cl)=NC2=C1N=CN2[C@@H]3O[C@H](CO)[C@@H](O)[C@@H]3F

InChI

InChIKey=WDDPHFBMKLOVOX-AYQXTPAHSA-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

HIDE SMILES / InChI

Molecular Formula C10H11ClFN5O3
Molecular Weight 303.677
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Clofarabine is a anti-cancer drug which was approved by FDA for the treatment of pediatric patients with relapsed or refractory acute lymphoblastic leukemia. After crossing the cell membrane the drug is rapidly metabolized by deoxycytidine kinase to diphosphate and triphosphate metabolites and these metabolites reversibly inhibit hRNR by binding to alpha subunit. Also the triphosphate is incorporated to DNA where it acts as a chain terminator.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
17.0 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CLOLAR

Cmax

ValueDoseCo-administeredAnalytePopulation
308 ng/mL
40 mg/m² 1 times / day multiple, intravenous
CLOFARABINE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
1793 ng × h/mL
40 mg/m² 1 times / day multiple, intravenous
CLOFARABINE plasma
Homo sapiens
28 ng × h/mL
40 mg/m² 1 times / day multiple, intravenous
CLOFARABINE blood
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
4.9 h
40 mg/m² 1 times / day multiple, intravenous
CLOFARABINE plasma
Homo sapiens
1.5 h
40 mg/m² 1 times / day multiple, intravenous
CLOFARABINE blood
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

Tox targets

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
The recommended pediatric dose is 52 mg/m2 given as an intravenous infusion over 2 hours daily for 5 consecutive days of a 28-day cycle. Repeat cycles every 2-6 week.
Route of Administration: Intravenous
In Vitro Use Guide
HL-60 cells or HL/ara-C20 cells were incubated with different concentrations of clofarabine for 72 h. The 50%-growth-inhibitory concentration IC50 was 50 nM for HL60 and 320 nM for HL/ara-C20 cells.
Substance Class Chemical
Record UNII
762RDY0Y2H
Record Status Validated (UNII)
Record Version