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Identification
NameClofarabine
Accession NumberDB00631  (APRD00878, DB07554)
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionClofarabine 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.
Structure
Thumb
Synonyms
(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-beta-D-arabinofuranosyl)adenine
2-chloro-9-(2'-Deoxy-2'-fluoro-beta-D-arabinofuranosyl)adenine
CAFdA
CL-F-Ara-a
Clofarabin
Clofarabina
Clofarabine
Clofarabinum
Clofarex
Clolar
External Identifiers
  • C1-F-Ara-A
  • CAfdA
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ClolarInjection1 mg/mLIntravenousSanofi Aventis U.S. Llc2013-04-01Not applicableUs
ClolarInjection1 mg/mLIntravenousGenzyme Corporation2004-12-28Not applicableUs
ClolarSolution1 mgIntravenousSanofi Aventis Canada Inc2010-02-10Not applicableCanada
EvoltraInjection, solution, concentrate1 mg/mlIntravenousGenzyme Europe B.V.2006-05-29Not applicableEu
EvoltraInjection, solution, concentrate1 mg/mlIntravenousGenzyme Europe B.V.2006-05-29Not applicableEu
EvoltraInjection, solution, concentrate1 mg/mlIntravenousGenzyme Europe B.V.2006-05-29Not applicableEu
EvoltraInjection, solution, concentrate1 mg/mlIntravenousGenzyme Europe B.V.2006-05-29Not applicableEu
EvoltraInjection, solution, concentrate1 mg/mlIntravenousGenzyme Europe B.V.2006-05-29Not applicableEu
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ClofazicRaffo
EvoltraGenzyme
Brand mixturesNot Available
SaltsNot Available
Categories
UNII762RDY0Y2H
CAS number123318-82-1
WeightAverage: 303.677
Monoisotopic: 303.053445155
Chemical FormulaC10H11ClFN5O3
InChI KeyWDDPHFBMKLOVOX-AYQXTPAHSA-N
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
IUPAC Name
(2R,3R,4S,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol
SMILES
[H][C@]1(F)[[email protected]](O)[C@@H](CO)O[[email protected]]1N1C=NC2=C(N)N=C(Cl)N=C12
Pharmacology
IndicationFor 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.
Structured Indications
PharmacodynamicsClofarabine 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.
Mechanism of actionClofarabine is metabolized intracellularly to the active 5'-monophosphate metabolite by deoxycytidine kinase and 5'-triphosphate metabolite by mono- and di-phospho-kinases. This metabolite inhibits DNA synthesis through an inhibitory action on ribonucleotide reductase, and by terminating DNA chain elongation and inhibiting repair through competitive inhibition of DNA polymerases. This leads to the depletion of the intracellular deoxynucleotide triphosphate pool and the self-potentiation of clofarabine triphosphate incorporation into DNA, thereby intensifying the effectiveness of DNA synthesis inhibition. The affinity of clofarabine triphosphate for these enzymes is similar to or greater than that of deoxyadenosine triphosphate. In preclinical models, clofarabine has demonstrated the ability to inhibit DNA repair by incorporation into the DNA chain during the repair process. Clofarabine 5'-triphosphate also disrupts the integrity of mitochondrial membrane, leading to the release of the pro-apoptotic mitochondrial proteins, cytochrome C and apoptosis-inducing factor, leading to programmed cell death.
TargetKindPharmacological actionActionsOrganismUniProt ID
DNA polymerase alpha catalytic subunitProteinyes
inhibitor
HumanP09884 details
Ribonucleoside-diphosphate reductase large subunitProteinyes
inhibitor
HumanP23921 details
DNANucleotideyes
other/unknown
Humannot applicabledetails
Related Articles
AbsorptionNot Available
Volume of distribution
  • 172 L/m2
Protein binding47% bound to plasma proteins, predominantly to albumin.
Metabolism

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.

SubstrateEnzymesProduct
Clofarabine
clofarabind-5'-monophosphateDetails
Route of eliminationBased on 24-hour urine collections in the pediatric studies, 49 - 60% of the dose is excreted in the urine unchanged.
Half lifeThe terminal half-life is estimated to be 5.2 hours.
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]
ToxicityThere 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Clofarabine.Approved
AcetazolamideThe risk or severity of adverse effects can be increased when Clofarabine is combined with Acetazolamide.Approved, Vet Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Clofarabine.Approved
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Clofarabine.Approved
AliskirenThe risk or severity of adverse effects can be increased when Aliskiren is combined with Clofarabine.Approved, Investigational
ALT-110The risk or severity of adverse effects can be increased when Clofarabine is combined with ALT-110.Investigational
AmifostineThe risk or severity of adverse effects can be increased when Amifostine is combined with Clofarabine.Approved, Investigational
AmilorideThe risk or severity of adverse effects can be increased when Amiloride is combined with Clofarabine.Approved
AmiodaroneThe risk or severity of adverse effects can be increased when Amiodarone is combined with Clofarabine.Approved, Investigational
AmlodipineThe risk or severity of adverse effects can be increased when Amlodipine is combined with Clofarabine.Approved
AmobarbitalAmobarbital may increase the hypotensive activities of Clofarabine.Approved, Illicit
Amphotericin BThe risk or severity of adverse effects can be increased when Amphotericin B is combined with Clofarabine.Approved, Investigational
Amyl NitriteThe risk or severity of adverse effects can be increased when Amyl Nitrite is combined with Clofarabine.Approved
AnvirzelAnvirzel may decrease the cardiotoxic activities of Clofarabine.Investigational
ApomorphineThe risk or severity of adverse effects can be increased when Apomorphine is combined with Clofarabine.Approved, Investigational
ApraclonidineThe risk or severity of adverse effects can be increased when Apraclonidine is combined with Clofarabine.Approved
AripiprazoleAripiprazole may increase the hypotensive activities of Clofarabine.Approved, Investigational
ArotinololThe risk or severity of adverse effects can be increased when Arotinolol is combined with Clofarabine.Approved
Arsenic trioxideThe risk or severity of adverse effects can be increased when Arsenic trioxide is combined with Clofarabine.Approved, Investigational
AtenololThe risk or severity of adverse effects can be increased when Atenolol is combined with Clofarabine.Approved
Azilsartan medoxomilThe risk or severity of adverse effects can be increased when Azilsartan medoxomil is combined with Clofarabine.Approved
BarbexacloneBarbexaclone may increase the hypotensive activities of Clofarabine.Experimental
BarbitalBarbital may increase the hypotensive activities of Clofarabine.Illicit
BarnidipineThe risk or severity of adverse effects can be increased when Barnidipine is combined with Clofarabine.Approved
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Clofarabine.Investigational
BenazeprilThe risk or severity of adverse effects can be increased when Benazepril is combined with Clofarabine.Approved, Investigational
BendroflumethiazideThe risk or severity of adverse effects can be increased when Bendroflumethiazide is combined with Clofarabine.Approved
BepridilThe risk or severity of adverse effects can be increased when Bepridil is combined with Clofarabine.Approved, Withdrawn
BetaxololThe risk or severity of adverse effects can be increased when Betaxolol is combined with Clofarabine.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Clofarabine.Approved, Investigational
BisoprololThe risk or severity of adverse effects can be increased when Bisoprolol is combined with Clofarabine.Approved
BortezomibThe risk or severity of adverse effects can be increased when Bortezomib is combined with Clofarabine.Approved, Investigational
BretyliumThe risk or severity of adverse effects can be increased when Bretylium is combined with Clofarabine.Approved
BrimonidineThe risk or severity of adverse effects can be increased when Brimonidine is combined with Clofarabine.Approved
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Clofarabine.Approved, Investigational
BumetanideThe risk or severity of adverse effects can be increased when Bumetanide is combined with Clofarabine.Approved
BupivacaineThe risk or severity of adverse effects can be increased when Bupivacaine is combined with Clofarabine.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Clofarabine.Approved
CanagliflozinThe risk or severity of adverse effects can be increased when Canagliflozin is combined with Clofarabine.Approved
CandesartanThe risk or severity of adverse effects can be increased when Candesartan is combined with Clofarabine.Approved
CaptoprilThe risk or severity of adverse effects can be increased when Captopril is combined with Clofarabine.Approved
CarbetocinThe risk or severity of adverse effects can be increased when Carbetocin is combined with Clofarabine.Approved
CarteololThe risk or severity of adverse effects can be increased when Carteolol is combined with Clofarabine.Approved
CarvedilolThe risk or severity of adverse effects can be increased when Carvedilol is combined with Clofarabine.Approved, Investigational
CDX-110The risk or severity of adverse effects can be increased when Clofarabine is combined with CDX-110.Investigational
ChlorothiazideThe risk or severity of adverse effects can be increased when Chlorothiazide is combined with Clofarabine.Approved, Vet Approved
ChlorpromazineThe risk or severity of adverse effects can be increased when Chlorpromazine is combined with Clofarabine.Approved, Vet Approved
ChlorthalidoneThe risk or severity of adverse effects can be increased when Chlorthalidone is combined with Clofarabine.Approved
CilazaprilThe risk or severity of adverse effects can be increased when Cilazapril is combined with Clofarabine.Approved
CilnidipineThe risk or severity of adverse effects can be increased when Cilnidipine is combined with Clofarabine.Approved
ClevidipineThe risk or severity of adverse effects can be increased when Clevidipine is combined with Clofarabine.Approved
ClomipramineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Clomipramine.Approved, Vet Approved
ClonidineThe risk or severity of adverse effects can be increased when Clonidine is combined with Clofarabine.Approved
ClozapineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Clozapine.Approved
ConivaptanThe risk or severity of adverse effects can be increased when Clofarabine is combined with Conivaptan.Approved, Investigational
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Clofarabine.Approved, Investigational
DapagliflozinThe risk or severity of adverse effects can be increased when Dapagliflozin is combined with Clofarabine.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Clofarabine.Approved
DesfluraneThe risk or severity of adverse effects can be increased when Clofarabine is combined with Desflurane.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Clofarabine.Approved
DexmedetomidineThe risk or severity of adverse effects can be increased when Dexmedetomidine is combined with Clofarabine.Approved, Vet Approved
DiclofenamideThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Clofarabine.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Clofarabine.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Clofarabine.Approved
DiltiazemThe risk or severity of adverse effects can be increased when Diltiazem is combined with Clofarabine.Approved
DinutuximabThe risk or severity of adverse effects can be increased when Dinutuximab is combined with Clofarabine.Approved
DipyridamoleThe risk or severity of adverse effects can be increased when Dipyridamole is combined with Clofarabine.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Clofarabine.Approved, Investigational
DoxazosinThe risk or severity of adverse effects can be increased when Doxazosin is combined with Clofarabine.Approved
DuloxetineClofarabine may increase the orthostatic hypotensive activities of Duloxetine.Approved
EfonidipineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Efonidipine.Approved
EltrombopagThe serum concentration of Clofarabine can be increased when it is combined with Eltrombopag.Approved
EmpagliflozinThe risk or severity of adverse effects can be increased when Empagliflozin is combined with Clofarabine.Approved
EnalaprilThe risk or severity of adverse effects can be increased when Enalapril is combined with Clofarabine.Approved, Vet Approved
EnalaprilatThe risk or severity of adverse effects can be increased when Clofarabine is combined with Enalaprilat.Approved
EplerenoneThe risk or severity of adverse effects can be increased when Eplerenone is combined with Clofarabine.Approved
EpoprostenolThe risk or severity of adverse effects can be increased when Clofarabine is combined with Epoprostenol.Approved
EprosartanThe risk or severity of adverse effects can be increased when Eprosartan is combined with Clofarabine.Approved
EsmololThe risk or severity of adverse effects can be increased when Esmolol is combined with Clofarabine.Approved
Etacrynic acidThe risk or severity of adverse effects can be increased when Etacrynic acid is combined with Clofarabine.Approved
FelodipineThe risk or severity of adverse effects can be increased when Felodipine is combined with Clofarabine.Approved, Investigational
FenoldopamThe risk or severity of adverse effects can be increased when Clofarabine is combined with Fenoldopam.Approved
FimasartanThe risk or severity of adverse effects can be increased when Clofarabine is combined with Fimasartan.Approved
FingolimodClofarabine may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
FosinoprilThe risk or severity of adverse effects can be increased when Fosinopril is combined with Clofarabine.Approved
FurosemideThe risk or severity of adverse effects can be increased when Furosemide is combined with Clofarabine.Approved, Vet Approved
G17DTThe risk or severity of adverse effects can be increased when Clofarabine is combined with G17DT.Investigational
GI-5005The risk or severity of adverse effects can be increased when Clofarabine is combined with GI-5005.Investigational
GuanfacineThe risk or severity of adverse effects can be increased when Guanfacine is combined with Clofarabine.Approved, Investigational
HalothaneThe risk or severity of adverse effects can be increased when Clofarabine is combined with Halothane.Approved, Vet Approved
HexobarbitalHexobarbital may increase the hypotensive activities of Clofarabine.Approved
HydralazineThe risk or severity of adverse effects can be increased when Hydralazine is combined with Clofarabine.Approved
HydrochlorothiazideThe risk or severity of adverse effects can be increased when Hydrochlorothiazide is combined with Clofarabine.Approved, Vet Approved
HydroflumethiazideThe risk or severity of adverse effects can be increased when Clofarabine is combined with Hydroflumethiazide.Approved
IloprostThe risk or severity of adverse effects can be increased when Clofarabine is combined with Iloprost.Approved, Investigational
ImidaprilThe risk or severity of adverse effects can be increased when Clofarabine is combined with Imidapril.Investigational
ImipramineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Imipramine.Approved
IndapamideThe risk or severity of adverse effects can be increased when Indapamide is combined with Clofarabine.Approved
IndoraminThe risk or severity of adverse effects can be increased when Clofarabine is combined with Indoramin.Withdrawn
INGN 201The risk or severity of adverse effects can be increased when Clofarabine is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Clofarabine is combined with INGN 225.Investigational
IrbesartanThe risk or severity of adverse effects can be increased when Irbesartan is combined with Clofarabine.Approved, Investigational
IsocarboxazidThe risk or severity of adverse effects can be increased when Clofarabine is combined with Isocarboxazid.Approved
IsofluraneThe risk or severity of adverse effects can be increased when Clofarabine is combined with Isoflurane.Approved, Vet Approved
Isosorbide DinitrateThe risk or severity of adverse effects can be increased when Isosorbide Dinitrate is combined with Clofarabine.Approved
Isosorbide MononitrateThe risk or severity of adverse effects can be increased when Isosorbide Mononitrate is combined with Clofarabine.Approved
IsoxsuprineThe risk or severity of adverse effects can be increased when Isoxsuprine is combined with Clofarabine.Approved, Withdrawn
IsradipineThe risk or severity of adverse effects can be increased when Isradipine is combined with Clofarabine.Approved
LabetalolThe risk or severity of adverse effects can be increased when Labetalol is combined with Clofarabine.Approved
LacidipineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Lacidipine.Approved
LeflunomideThe risk or severity of adverse effects can be increased when Clofarabine is combined with Leflunomide.Approved, Investigational
LercanidipineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Lercanidipine.Approved, Investigational
LevobunololThe risk or severity of adverse effects can be increased when Levobunolol is combined with Clofarabine.Approved
LevobupivacaineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Levobupivacaine.Approved
LevodopaClofarabine may increase the orthostatic hypotensive activities of Levodopa.Approved
LevosimendanThe risk or severity of adverse effects can be increased when Clofarabine is combined with Levosimendan.Approved, Investigational
LisinoprilThe risk or severity of adverse effects can be increased when Lisinopril is combined with Clofarabine.Approved, Investigational
LofexidineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Lofexidine.Approved, Investigational
LosartanThe risk or severity of adverse effects can be increased when Losartan is combined with Clofarabine.Approved
MannitolThe risk or severity of adverse effects can be increased when Mannitol is combined with Clofarabine.Approved, Investigational
MecamylamineThe risk or severity of adverse effects can be increased when Mecamylamine is combined with Clofarabine.Approved
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Clofarabine.Withdrawn
MethazolamideThe risk or severity of adverse effects can be increased when Methazolamide is combined with Clofarabine.Approved
MethohexitalMethohexital may increase the hypotensive activities of Clofarabine.Approved
MethyclothiazideThe risk or severity of adverse effects can be increased when Methyclothiazide is combined with Clofarabine.Approved
MethyldopaThe risk or severity of adverse effects can be increased when Methyldopa is combined with Clofarabine.Approved
MethylphenobarbitalMethylphenobarbital may increase the hypotensive activities of Clofarabine.Approved
MetipranololThe risk or severity of adverse effects can be increased when Metipranolol is combined with Clofarabine.Approved
MetolazoneThe risk or severity of adverse effects can be increased when Metolazone is combined with Clofarabine.Approved
MetoprololThe risk or severity of adverse effects can be increased when Metoprolol is combined with Clofarabine.Approved, Investigational
MinoxidilThe risk or severity of adverse effects can be increased when Minoxidil is combined with Clofarabine.Approved
MoexiprilThe risk or severity of adverse effects can be increased when Moexipril is combined with Clofarabine.Approved
MorphineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Morphine.Approved, Investigational
MoxonidineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Moxonidine.Approved
NabiloneThe risk or severity of adverse effects can be increased when Clofarabine is combined with Nabilone.Approved, Investigational
NadololThe risk or severity of adverse effects can be increased when Nadolol is combined with Clofarabine.Approved
NatalizumabThe risk or severity of adverse effects can be increased when Clofarabine is combined with Natalizumab.Approved, Investigational
NebivololThe risk or severity of adverse effects can be increased when Nebivolol is combined with Clofarabine.Approved, Investigational
NesiritideThe risk or severity of adverse effects can be increased when Nesiritide is combined with Clofarabine.Approved, Investigational
NicardipineThe risk or severity of adverse effects can be increased when Nicardipine is combined with Clofarabine.Approved
NicorandilNicorandil may increase the hypotensive activities of Clofarabine.Approved
NifedipineThe risk or severity of adverse effects can be increased when Nifedipine is combined with Clofarabine.Approved
NilvadipineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Nilvadipine.Approved
NimodipineThe risk or severity of adverse effects can be increased when Nimodipine is combined with Clofarabine.Approved
NisoldipineThe risk or severity of adverse effects can be increased when Nisoldipine is combined with Clofarabine.Approved
NitrendipineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Nitrendipine.Approved
Nitric OxideThe risk or severity of adverse effects can be increased when Clofarabine is combined with Nitric Oxide.Approved
NitroglycerinThe risk or severity of adverse effects can be increased when Nitroglycerin is combined with Clofarabine.Approved, Investigational
NitroprussideThe risk or severity of adverse effects can be increased when Nitroprusside is combined with Clofarabine.Approved
ObinutuzumabThe risk or severity of adverse effects can be increased when Clofarabine is combined with Obinutuzumab.Approved
OlmesartanThe risk or severity of adverse effects can be increased when Olmesartan is combined with Clofarabine.Approved, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Clofarabine.Approved
OxprenololThe risk or severity of adverse effects can be increased when Clofarabine is combined with Oxprenolol.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Clofarabine.Approved, Vet Approved
PapaverineThe risk or severity of adverse effects can be increased when Papaverine is combined with Clofarabine.Approved
PenbutololThe risk or severity of adverse effects can be increased when Penbutolol is combined with Clofarabine.Approved, Investigational
PentobarbitalPentobarbital may increase the hypotensive activities of Clofarabine.Approved, Vet Approved
PerindoprilThe risk or severity of adverse effects can be increased when Perindopril is combined with Clofarabine.Approved
PhenelzineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Phenelzine.Approved
PhenobarbitalPhenobarbital may increase the hypotensive activities of Clofarabine.Approved
PhenoxybenzamineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Phenoxybenzamine.Approved
PhentolamineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Phentolamine.Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Clofarabine.Approved, Investigational
PindololThe risk or severity of adverse effects can be increased when Pindolol is combined with Clofarabine.Approved
PipamperoneThe risk or severity of adverse effects can be increased when Clofarabine is combined with Pipamperone.Approved
PramipexoleThe risk or severity of adverse effects can be increased when Clofarabine is combined with Pramipexole.Approved, Investigational
PrazosinThe risk or severity of adverse effects can be increased when Prazosin is combined with Clofarabine.Approved
PrimidonePrimidone may increase the hypotensive activities of Clofarabine.Approved, Vet Approved
PropofolThe risk or severity of adverse effects can be increased when Clofarabine is combined with Propofol.Approved, Investigational, Vet Approved
PropranololThe risk or severity of adverse effects can be increased when Propranolol is combined with Clofarabine.Approved, Investigational
QuetiapineThe risk or severity of adverse effects can be increased when Quetiapine is combined with Clofarabine.Approved
QuinaprilThe risk or severity of adverse effects can be increased when Quinapril is combined with Clofarabine.Approved, Investigational
Rabies vaccineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Rabies vaccine.Approved
Rabies vaccineThe therapeutic efficacy of Rabies vaccine can be decreased when used in combination with Clofarabine.Approved
RamiprilThe risk or severity of adverse effects can be increased when Ramipril is combined with Clofarabine.Approved
RasagilineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Rasagiline.Approved
RemifentanilThe risk or severity of adverse effects can be increased when Clofarabine is combined with Remifentanil.Approved
ReserpineThe risk or severity of adverse effects can be increased when Reserpine is combined with Clofarabine.Approved
RiociguatThe risk or severity of adverse effects can be increased when Riociguat is combined with Clofarabine.Approved
RisperidoneClofarabine may increase the hypotensive activities of Risperidone.Approved, Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Clofarabine.Approved
RolapitantThe serum concentration of Clofarabine can be increased when it is combined with Rolapitant.Approved
RopiniroleThe risk or severity of adverse effects can be increased when Clofarabine is combined with Ropinirole.Approved, Investigational
RopivacaineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Ropivacaine.Approved
RotigotineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Rotigotine.Approved
SacubitrilThe risk or severity of adverse effects can be increased when Clofarabine is combined with Sacubitril.Approved
SecobarbitalSecobarbital may increase the hypotensive activities of Clofarabine.Approved, Vet Approved
SelegilineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Selegiline.Approved, Investigational, Vet Approved
SevofluraneThe risk or severity of adverse effects can be increased when Clofarabine is combined with Sevoflurane.Approved, Vet Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Clofarabine.Approved
Sodium NitriteThe risk or severity of adverse effects can be increased when Clofarabine is combined with Sodium Nitrite.Approved
SotalolThe risk or severity of adverse effects can be increased when Sotalol is combined with Clofarabine.Approved
SpironolactoneThe risk or severity of adverse effects can be increased when Spironolactone is combined with Clofarabine.Approved
SRP 299The risk or severity of adverse effects can be increased when Clofarabine is combined with SRP 299.Investigational
StreptokinaseThe risk or severity of adverse effects can be increased when Clofarabine is combined with Streptokinase.Approved
SufentanilThe risk or severity of adverse effects can be increased when Clofarabine is combined with Sufentanil.Approved, Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Clofarabine.Approved, Investigational
TamsulosinThe risk or severity of adverse effects can be increased when Clofarabine is combined with Tamsulosin.Approved, Investigational
TelmisartanThe risk or severity of adverse effects can be increased when Telmisartan is combined with Clofarabine.Approved, Investigational
TerazosinThe risk or severity of adverse effects can be increased when Terazosin is combined with Clofarabine.Approved
TeriflunomideThe serum concentration of Clofarabine can be increased when it is combined with Teriflunomide.Approved
TG4010The risk or severity of adverse effects can be increased when Clofarabine is combined with TG4010.Investigational
ThalidomideThe risk or severity of adverse effects can be increased when Clofarabine is combined with Thalidomide.Approved, Investigational, Withdrawn
ThiamylalThiamylal may increase the hypotensive activities of Clofarabine.Approved, Vet Approved
ThiopentalThiopental may increase the hypotensive activities of Clofarabine.Approved, Vet Approved
ThioridazineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Thioridazine.Approved
TimololThe risk or severity of adverse effects can be increased when Timolol is combined with Clofarabine.Approved
TizanidineThe risk or severity of adverse effects can be increased when Tizanidine is combined with Clofarabine.Approved
TofacitinibClofarabine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TolazolineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Tolazoline.Approved, Vet Approved
TolcaponeThe risk or severity of adverse effects can be increased when Clofarabine is combined with Tolcapone.Approved, Withdrawn
TorasemideThe risk or severity of adverse effects can be increased when Torasemide is combined with Clofarabine.Approved
TrandolaprilThe risk or severity of adverse effects can be increased when Trandolapril is combined with Clofarabine.Approved
TranylcypromineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Tranylcypromine.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Clofarabine.Approved, Investigational
TretinoinThe risk or severity of adverse effects can be increased when Clofarabine is combined with Tretinoin.Approved, Investigational, Nutraceutical
TriamtereneThe risk or severity of adverse effects can be increased when Triamterene is combined with Clofarabine.Approved
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Clofarabine.Approved, Investigational
VerapamilThe risk or severity of adverse effects can be increased when Verapamil is combined with Clofarabine.Approved
Food Interactions
  • Echinacea should be used with caution, if at all, in patients receiving therapeutic immunosuppressants. Monitor for reduced efficacy of the immunosuppressant during concomitant use.
References
Synthesis ReferenceNot Available
General References
  1. Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. [PubMed:20631817 ]
  2. Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. [PubMed:18728851 ]
  3. 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:19519505 ]
  4. Larson ML, Venugopal P: Clofarabine: a new treatment option for patients with acute myeloid leukemia. Expert Opin Pharmacother. 2009 Jun;10(8):1353-7. doi: 10.1517/14656560902997990. [PubMed:19463072 ]
  5. 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. doi: 10.1016/j.bcp.2009.06.094. Epub 2009 Jul 1. [PubMed:19576186 ]
External Links
ATC CodesL01BB06
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (281 KB)
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9827
Caco-2 permeable-0.7369
P-glycoprotein substrateNon-substrate0.8001
P-glycoprotein inhibitor INon-inhibitor0.9382
P-glycoprotein inhibitor IINon-inhibitor0.8279
Renal organic cation transporterNon-inhibitor0.9144
CYP450 2C9 substrateNon-substrate0.9031
CYP450 2D6 substrateNon-substrate0.8291
CYP450 3A4 substrateNon-substrate0.5681
CYP450 1A2 substrateNon-inhibitor0.817
CYP450 2C9 inhibitorNon-inhibitor0.8462
CYP450 2D6 inhibitorNon-inhibitor0.8849
CYP450 2C19 inhibitorNon-inhibitor0.8391
CYP450 3A4 inhibitorNon-inhibitor0.8499
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9002
Ames testNon AMES toxic0.7338
CarcinogenicityNon-carcinogens0.7723
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.2651 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9643
hERG inhibition (predictor II)Non-inhibitor0.8304
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Genzyme corp
Packagers
Dosage forms
FormRouteStrength
InjectionIntravenous1 mg/mL
SolutionIntravenous1 mg
Injection, solution, concentrateIntravenous1 mg/ml
Prices
Unit descriptionCostUnit
Clolar 20 mg/20 ml vial135.0USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2102782 No2003-09-162012-05-07Canada
US5661136 Yes1998-07-142018-07-14Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP0Not Available
Predicted Properties
PropertyValueSource
Water Solubility4.89 mg/mLALOGPS
logP0.32ALOGPS
logP-0.29ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)12.71ChemAxon
pKa (Strongest Basic)1.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area119.31 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity67 m3·mol-1ChemAxon
Polarizability26.06 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as purine 3'-deoxyribonucleosides. These are compounds consisting of a purine linked to a ribose which lacks a hydroxyl group at position 3.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassPurine nucleosides
Sub ClassPurine 3'-deoxyribonucleosides
Direct ParentPurine 3'-deoxyribonucleosides
Alternative Parents
Substituents
  • Purine 3'-deoxyribonucleoside
  • Purine 2'-deoxyribonucleoside
  • 6-aminopurine
  • Purine
  • Imidazopyrimidine
  • Halopyrimidine
  • Aminopyrimidine
  • Imidolactam
  • Pyrimidine
  • Primary aromatic amine
  • N-substituted imidazole
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Oxolane
  • Imidazole
  • Azole
  • Secondary alcohol
  • Halohydrin
  • Fluorohydrin
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Primary amine
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organochloride
  • Organohalogen compound
  • Amine
  • Alkyl halide
  • Alkyl fluoride
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Protein kinase binding
Specific Function:
Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha com...
Gene Name:
POLA1
Uniprot ID:
P09884
Molecular Weight:
165911.405 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. [PubMed:20631817 ]
  4. Authors unspecified: Clofarabine. Drugs R D. 2004;5(4):213-7. [PubMed:15230627 ]
  5. Musto P, Ferrara F: Clofarabine: in search of combinations for the treatment of patients with high-risk acute myeloid leukemia. Cancer. 2008 Oct 15;113(8):1995-8. doi: 10.1002/cncr.23804. [PubMed:18780321 ]
  6. Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. [PubMed:18728851 ]
  7. Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. [PubMed:17852710 ]
  8. 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:19519505 ]
  9. 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. doi: 10.1016/j.bcp.2009.06.094. Epub 2009 Jul 1. [PubMed:19576186 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
Specific Function:
Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
Gene Name:
RRM1
Uniprot ID:
P23921
Molecular Weight:
90069.375 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. [PubMed:20631817 ]
  4. Authors unspecified: Clofarabine. Drugs R D. 2004;5(4):213-7. [PubMed:15230627 ]
  5. Musto P, Ferrara F: Clofarabine: in search of combinations for the treatment of patients with high-risk acute myeloid leukemia. Cancer. 2008 Oct 15;113(8):1995-8. doi: 10.1002/cncr.23804. [PubMed:18780321 ]
  6. Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. [PubMed:18728851 ]
  7. Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. [PubMed:17852710 ]
  8. 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:19519505 ]
  9. 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. doi: 10.1016/j.bcp.2009.06.094. Epub 2009 Jul 1. [PubMed:19576186 ]
3. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
other/unknown
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. [PubMed:20631817 ]
  2. Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. [PubMed:18728851 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Protein homodimerization activity
Specific Function:
Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.
Gene Name:
DCK
Uniprot ID:
P27707
Molecular Weight:
30518.315 Da
References
  1. Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. [PubMed:20631817 ]
  2. 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. doi: 10.1016/j.bcp.2009.06.094. Epub 2009 Jul 1. [PubMed:19576186 ]
  3. Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. [PubMed:17852710 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular Weight:
72313.47 Da
References
  1. de Wolf C, Jansen R, Yamaguchi H, de Haas M, van de Wetering K, Wijnholds J, Beijnen J, Borst P: Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides. Mol Cancer Ther. 2008 Sep;7(9):3092-102. doi: 10.1158/1535-7163.MCT-08-0427. Epub 2008 Sep 2. [PubMed:18765824 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on December 05, 2016 03:58