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

Details

Stereochemistry ABSOLUTE
Molecular Formula C10H12ClN5O3
Molecular Weight 285.687
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CLADRIBINE

SMILES

NC1=NC(Cl)=NC2=C1N=CN2[C@H]3C[C@H](O)[C@@H](CO)O3

InChI

InChIKey=PTOAARAWEBMLNO-KVQBGUIXSA-N
InChI=1S/C10H12ClN5O3/c11-10-14-8(12)7-9(15-10)16(3-13-7)6-1-4(18)5(2-17)19-6/h3-6,17-18H,1-2H2,(H2,12,14,15)/t4-,5+,6+/m0/s1

HIDE SMILES / InChI

Molecular Formula C10H12ClN5O3
Molecular Weight 285.687
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created using several sources including: https://www.scripps.edu/newsandviews/e_20090601/MS.html; http://comtecmed.com/CONY/2008/Uploads/assets/speakers%20abstracts/stelmasiak.pdf

Cladribine is used for the treatment of hairy cell leukemia and multiple sclerosis (MS). As a purine analog, it is a synthetic anti-cancer agent that also suppresses the immune system. Chemically, it mimics the nucleoside adenosine and thus inhibits the enzyme adenosine deaminase, which interferes with the cell's ability to process DNA. It can be distinguished from other chemotherapeutic agents affecting purine metabolism in that it is cytotoxic to both actively dividing and quiescent lymphocytes and monocytes, inhibiting both DNA synthesis and repair. Cladribine injection is a potent antineoplastic agent with potentially significant toxic side effects. In MS, the novel mechanism of action of cladribine is expected to reduce inflammation, autoimmune effects and autoreactive cell damage, thereby improving the integrity of the blood–brain barrier. Thus, the effects of cladribine may target some of the key events that are central to the pathophysiology of MS.

CNS Activity

Curator's Comment: As cladribine can cross the blood brain barrier and can kill dividing and non-dividing T and B cells and can apparently kill plasma cells. It could target plasma cells in the brain, unlike any other MS drug.

Originator

Curator's Comment: The drug, cladribine, which is currently marketed under the name LEUSTATIN® by Ortho Biotech, Inc. (an affiliate of Johnson & Johnson) for the treatment of hairy cell leukemia, was initially identified and developed using a single treatment of the new compound to target abnormal white blood cells in patients suffering from hairy cell leukemia by Dennis Carson in collaboration with Ernest Beutler a Scripps Research scientists who licensed caldribine as an orphan drug in 1994. Merck Serono's CLARITY study, involving 1326 Multiple Sclerosis patients, began in 2004 and was completed in December 2008.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P06746
Gene ID: 5423.0
Gene Symbol: POLB
Target Organism: Homo sapiens (Human)
Target ID: P23526
Gene ID: 191.0
Gene Symbol: AHCY
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CLADRIBINE

Approved Use

the treatment of active Hairy Cell Leukemia as defined by clinically significant anemia, neutropenia, thrombocytopenia or disease-related symptoms.

Launch Date

7.9185602E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
20.57 ng/mL
3 mg single, intravenous
dose: 3 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CLADRIBINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
29.05 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLADRIBINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
69.4 ng × h/mL
3 mg single, intravenous
dose: 3 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CLADRIBINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
99.17 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLADRIBINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
18.4 h
3 mg single, intravenous
dose: 3 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CLADRIBINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
19.7 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLADRIBINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
5.25 mg/kg multiple, oral (total)
Highest studied dose
Dose: 5.25 mg/kg
Route: oral
Route: multiple
Dose: 5.25 mg/kg
Sources: Page: p.262
unhealthy, ADULT
n = 204
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 204
Sources: Page: p.262
Disc. AE: Lymphopenia...
AEs leading to
discontinuation/dose reduction:
Lymphopenia (grade 3-4)
Sources: Page: p.262
8 mg/m2 1 times / day multiple, intravenous
MTD
Dose: 8 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 8 mg/m2, 1 times / day
Sources: Page: p.170
unhealthy, ADULT
n = 4
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 4
Sources: Page: p.170
DLT: Neutropenia, Leukopenia...
Dose limiting toxicities:
Neutropenia (grade 4, 50%)
Leukopenia (grade 4, 50%)
Sources: Page: p.170
0.07 mg/kg 1 times / day multiple, subcutaneous
Studied dose
Dose: 0.07 mg/kg, 1 times / day
Route: subcutaneous
Route: multiple
Dose: 0.07 mg/kg, 1 times / day
Sources: Page: p.1152
unhealthy, ADULT
n = 52
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 52
Sources: Page: p.1152
AEs

AEs

AESignificanceDosePopulation
Lymphopenia grade 3-4
Disc. AE
5.25 mg/kg multiple, oral (total)
Highest studied dose
Dose: 5.25 mg/kg
Route: oral
Route: multiple
Dose: 5.25 mg/kg
Sources: Page: p.262
unhealthy, ADULT
n = 204
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 204
Sources: Page: p.262
Leukopenia grade 4, 50%
DLT
8 mg/m2 1 times / day multiple, intravenous
MTD
Dose: 8 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 8 mg/m2, 1 times / day
Sources: Page: p.170
unhealthy, ADULT
n = 4
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 4
Sources: Page: p.170
Neutropenia grade 4, 50%
DLT
8 mg/m2 1 times / day multiple, intravenous
MTD
Dose: 8 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 8 mg/m2, 1 times / day
Sources: Page: p.170
unhealthy, ADULT
n = 4
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 4
Sources: Page: p.170
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Severe skin rash in two consecutive patients treated with 2-chlorodeoxyadenosine for hairy cell leukaemia at a single institution.
2000 Apr
Guillain-Barre syndrome following 2-chlorodeoxyadenosine treatment for Hairy Cell Leukemia.
2000 Nov
[Nucleoside analogues--new drugs for the treatment of lymphatic cancers].
2001
[Lupus nephritis: treatments for today and tomorrow].
2001
Immunomodulatory drugs for multiple sclerosis: a systematic review of clinical and cost effectiveness.
2001 Apr
Langerhans cell histiocytosis: central nervous system involvement treated successfully with 2-chlorodeoxyadenosine.
2001 Apr-May
A phase II study of sequential combination chemotherapy with cyclophosphamide, prednisone, and 2-chlorodeoxyadenosine in previously untreated patients with chronic lymphocytic leukemia.
2001 Aug
Cladribine. Ortho Biotech Inc.
2001 Dec
Hematological effects of intermittent 2-hour infusions of cladribine in multiple sclerosis patients: a comparison of 2 dosage patterns.
2001 Dec
Second primary tumors and immune phenomena after fludarabine or 2-chloro-2'-deoxyadenosine treatment.
2001 Feb
Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation.
2001 Feb 1
Hairy cell leukemia.
2001 Jun
Nucleoside analogues: mechanisms of drug resistance and reversal strategies.
2001 Jun
Experience with 2-chlorodeoxyadenosine in previously untreated children with newly diagnosed acute myeloid leukemia and myelodysplastic diseases.
2001 Jun 1
Cladribine in combination with mitoxantrone and cyclophosphamide(CMC) in the treatment of heavily pre-treated patients with advanced indolent lymphoid malignancies.
2001 Mar
Effective treatment with rituximab in a patient with refractory prolymphocytoid transformed B-chronic lymphocytic leukemia and Evans syndrome.
2001 Mar
Immunosuppressive and cytotoxic drugs in the treatment of rheumatic skin disorders.
2001 Mar
Immunologic therapy for secondary and primary progressive multiple sclerosis.
2001 May
Plasmablastic lymphoma in a patient with chronic lymphocytic leukemia heavily pretreated with cladribine (2-CdA): an unusual variant of Richter's syndrome.
2001 Nov-Dec
Efficacy of anti-CD20 monoclonal antibodies (Mabthera) in patients with progressed hairy cell leukemia.
2001 Oct
Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy in chronic lymphocytic leukemia.
2001 Oct
In vitro release of cytotoxic nucleoside analogs from lactide-caprolactone and lactide-glycolide copolymers.
2002
5'-Esters of 2'-deoxyadenosine and 2-chloro-2'-deoxyadenosine with cell differentiation-provoking agents.
2002
Therapeutic approaches in multiple sclerosis: lessons from failed and interrupted treatment trials.
2002
Immunosuppression with limited toxicity: the characteristics of nucleoside analogs and anti-lymphocyte antibodies used in non-myeloablative hematopoietic cell transplantation.
2002
Gateways to Clinical Trials.
2002 Apr
Simultaneous diagnosis of hairy cell leukemia and chronic lymphocytic leukemia/small lymphocytic lymphoma: a frequent association?
2002 Aug
Use of 2-chlorodeoxyadenosine to treat infantile myofibromatosis.
2002 Jan
Bax expression correlates with cellular drug sensitivity to doxorubicin, cyclophosphamide and chlorambucil but not fludarabine, cladribine or corticosteroids in B cell chronic lymphocytic leukemia.
2002 Jun
Alkylating agents and nucleoside analogues in the treatment of B cell chronic lymphocytic leukemia.
2002 Jun
Oral cladribine for B-cell chronic lymphocytic leukaemia: report of a phase II trial with a 3-d, 3-weekly schedule in untreated and pretreated patients, and a long-term follow-up of 126 previously untreated patients.
2002 Mar
[Therapeutic effectiveness of cladribine and cellular immunodeficiency--related effects in hairy-cell leukemia?].
2002 May
Aggressive growth of epithelial carcinomas following treatment with nucleoside analogues.
2002 May
Adenine and deazaadenine nucleoside and deoxynucleoside analogues: inhibition of viral replication of sheep MVV (in vitro model for HIV) and bovine BHV-1.
2002 Sep
Patents

Sample Use Guides

In Vivo Use Guide
Sources: www.accessdata.fda.gov/drugsatfda_docs/label/2012/020229s034lbl.pdf
0.09 mg/kg/day
Route of Administration: Intravenous
In Vitro Use Guide
Curator's Comment: The lethal dose of cytarabine for CTRL cells (Mantle cell lymphoma cell line ) ranged from 0.05 to 0.4 μM determined in In vitro cytotoxicity assay that was used to analyze cells relative responsiveness to araC (cladribine).
0.05 - 0.4 uM
Substance Class Chemical
Created
by admin
on Fri Dec 16 15:57:02 UTC 2022
Edited
by admin
on Fri Dec 16 15:57:02 UTC 2022
Record UNII
47M74X9YT5
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CLADRIBINE
EMA EPAR   EP   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
CLADRIBINE [HSDB]
Common Name English
CLADRIBINE [EP MONOGRAPH]
Common Name English
MAVENCLAD
Common Name English
2-CHLORODEOXYADENOSINE
Systematic Name English
2-CDA
Common Name English
CLADRIBINE [USP MONOGRAPH]
Common Name English
CLADRIBINE [USP-RS]
Common Name English
LITAK
Brand Name English
cladribine [INN]
Common Name English
CLADRIBINE [MART.]
Common Name English
Cladribine [WHO-DD]
Common Name English
ADENOSINE, 2-CHLORO-2'-DEOXY-
Systematic Name English
2-CHLORO-2'-DEOXYADENOSINE
Systematic Name English
CLADRIBINE [ORANGE BOOK]
Common Name English
NSC-105014
Code English
CLADRIBINE [EMA EPAR]
Common Name English
LEUSTATIN
Brand Name English
CLADRIBINE [MI]
Common Name English
CLADRIBINE [VANDF]
Common Name English
CLADRIBINE [JAN]
Common Name English
RWJ-26251
Code English
CLADRIBINE [USP IMPURITY]
Common Name English
CLADRIBINE [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2157
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
FDA ORPHAN DRUG 54190
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
FDA ORPHAN DRUG 51690
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
WHO-VATC QL01BB04
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
EU-Orphan Drug EU/3/01/055
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
EMA ASSESSMENT REPORTS LITAK (AUTHORIZED: LEUKEMIA, HAIRY CELL)
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
FDA ORPHAN DRUG 467214
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
LIVERTOX NBK548555
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
FDA ORPHAN DRUG 68092
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
NCI_THESAURUS C1556
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
FDA ORPHAN DRUG 77793
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
WHO-ATC L04AA40
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
NCI_THESAURUS C798
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
FDA ORPHAN DRUG 47990
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
NDF-RT N0000175712
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
WHO-ATC L01BB04
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
Code System Code Type Description
DRUG CENTRAL
667
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
LACTMED
Cladribine
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
DAILYMED
47M74X9YT5
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
ChEMBL
CHEMBL1619
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
CHEBI
567361
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
WIKIPEDIA
CLADRIBINE
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
FDA UNII
47M74X9YT5
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
MESH
D017338
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
RXCUI
44157
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY RxNorm
DRUG BANK
DB00242
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
CAS
4291-63-8
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
EPA CompTox
DTXSID8022828
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
USAN
DD-79
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
EVMPD
SUB06635MIG
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
PUBCHEM
20279
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
IUPHAR
4799
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
RS_ITEM_NUM
1134200
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
NSC
105014
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
MERCK INDEX
M3606
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY Merck Index
INN
6997
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
NCI_THESAURUS
C1336
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
HSDB
7564
Created by admin on Fri Dec 16 15:57:02 UTC 2022 , Edited by admin on Fri Dec 16 15:57:02 UTC 2022
PRIMARY
Related Record Type Details
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
TARGET -> INHIBITOR
TARGET -> INHIBITOR
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (TLC)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC