CLOFARABINE

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

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 Target	Pharmacology	Condition	Potency
DNA 278	Binding Agent 1,064
Ribonucleoside-diphosphate reductase RR1 14	Inhibitor 8,297		17.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Relapsed or refractory acute lymphoblastic leukemia 2	Primary		Approved 8,429	CLOLAR

C_max

Value	Dose	Co-administered	Analyte	Population
308 ng/mL	40 mg/m² 1 times / day multiple, intravenous	CYTARABINE	CLOFARABINE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
1793 ng × h/mL	40 mg/m² 1 times / day multiple, intravenous	CYTARABINE	CLOFARABINE plasma	Homo sapiens
28 ng × h/mL	40 mg/m² 1 times / day multiple, intravenous		CLOFARABINE blood	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.9 h	40 mg/m² 1 times / day multiple, intravenous	CYTARABINE	CLOFARABINE plasma	Homo sapiens
1.5 h	40 mg/m² 1 times / day multiple, intravenous		CLOFARABINE blood	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
55 mg/m2 1 times / day multiple, intravenous Highest studied dose	unhealthy, 42 years n = 4	Other AEs: Nausea, Diarrhea...
40 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, 42 years n = 31	Other AEs: Nausea, Fatigue...
2 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, 51 years n = 6	DLT: Myelosuppression...
6 mg 1 times / day multiple, oral Highest studied dose	unhealthy, 60-76 years n = 1	Other AEs: Nausea, Hypoalbuminemia...
70 mg/m2 1 times / day multiple, intravenous Highest studied dose	unhealthy, child n = 2	Other AEs: Hyperbilirubinemia, Vomiting...

Showing 1 to 5 of 5 entries

Previous1Next

AEs

Show entries

AE	Significance	Dose	Population
Diarrhea	grade 1, 3 patients	55 mg/m2 1 times / day multiple, intravenous Highest studied dose	unhealthy, 42 years n = 4
Nausea	grade 1-2, 2 patients	55 mg/m2 1 times / day multiple, intravenous Highest studied dose	unhealthy, 42 years n = 4
Hepatotoxicity	grade 3, 2 patients	55 mg/m2 1 times / day multiple, intravenous Highest studied dose	unhealthy, 42 years n = 4
Anorexia	grade 1, 1 patient	40 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, 42 years n = 31
Cramp	grade 1, 1 patient	40 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, 42 years n = 31

Showing 1 to 5 of 19 entries

Previous1 2 3 4Next

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1,612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP450 65

Drug as victim

Show entries

Target	Modality	Activity	Metabolite	Clinical evidence
CYP450 65	substrate 3,367	no

Showing 1 to 1 of 1 entries

Previous1Next

Tox targets

Show entries

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1,647	inhibitor 1,626

Showing 1 to 1 of 1 entries

Previous1Next

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:681569	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:681569
MolPort	MolPort-005-941-711	https://www.molport.com/shop/molecule-link/MolPort-005-941-711
Selleck Chemicals	Clofarabine	http://www.selleckchem.com/products/Clofarabine.html
ZINC	ZINC000003798247	http://zinc15.docking.org/substances/ZINC000003798247
eMolecules	29256989	https://www.emolecules.com/cgi-bin/more?vid=29256989

Showing 1 to 5 of 6 entries

Previous1 2Next

PubMed

Show entries

Title	Date	PubMed
Gateways to Clinical Trials.	2002 Apr	12087878
Gateways to clinical trials.	2003 Jul-Aug	12949633
Bibliography. Current world literature. Therapeutic modalities.	2004 Nov	15643694
Complete remission following clofarabine treatment in refractory juvenile myelomonocytic leukemia.	2005 Mar	15750451
The role of clofarabine in hematologic and solid malignancies--development of a next-generation nucleoside analog.	2005 May 15	15803490

Showing 1 to 5 of 11 entries

Previous1 2 3Next

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

Show entries

Name

Type

Language

CLOFARABINE

Official Name

English

CLOFARABINE [VANDF]

Common Name

English

CLOFARABINE [MI]

Common Name

English

9H-PURIN-6-AMINE, 2-CHLORO-9-(2-DEOXY-2-FLUORO-.BETA.-D-ARABINOFURANOSYL)

Common Name

English

CLOLAR

Brand Name

English

Showing 1 to 5 of 15 entries

Previous1 2 3Next

Show entries

Classification Tree

Code System

Code

Designated

FDA ORPHAN DRUG

668118

Enzyme Inhibitors

NDF-RT

N0000000233

Designated/Approved

FDA ORPHAN DRUG

153201

Antimetabolite

NCI_THESAURUS

C1556

Purine analogues

WHO-VATC

QL01BB06

Showing 1 to 5 of 11 entries

Previous1 2 3Next

Show entries

Code System

Code

Type

Description

RXCUI

44151

PRIMARY

RxNorm

FDA UNII

762RDY0Y2H

PRIMARY

NSC

759857

PRIMARY

EPA CompTox

DTXSID5046437

PRIMARY

DRUG BANK

DB00631

PRIMARY

Showing 1 to 5 of 22 entries

Previous1 2 3 4 5Next

Show entries

Related Record

Type

Details


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Interaction Type:

BINDING

Amount:

47 % (average)


					9UK37YB4S2

CLOFARABINE F-18

LABELED -> NON-LABELED

Amount:

Showing 1 to 2 of 2 entries

Previous1Next

Show entries

Related Record

Type

Details


					YPJ8ZV99ZP

Clofarabine triphosphate

METABOLITE ACTIVE -> PRODRUG

Amount:

Showing 1 to 1 of 1 entries

Previous1Next

Show entries

Related Record

Type

Details


					YPJ8ZV99ZP

Clofarabine triphosphate

ACTIVE MOIETY

Amount:

Showing 1 to 1 of 1 entries

Previous1Next

Name	Property Type	Amount	Referenced Substance	Defining	Parameters	References
Biological Half-life	PHARMACOKINETIC	5.2 hours (average)

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Doses

AEs

Overview

OverviewOther

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2