CLADRIBINE

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 Search

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
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020229s034lbl.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA polymerase beta 5 Target ID: P06746 Gene ID: 5423.0 Gene Symbol: POLB Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=20634380	Inhibitor 8146
DNA 241 Target ID: CHEMBL2311221 Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=20634380	Binding Agent 1037
Adenosylhomocysteinase 5 Target ID: P23526 Gene ID: 191.0 Gene Symbol: AHCY Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=20634380	Inhibitor 8146

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hairy cell leukemia 2 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a2592a9b-bca6-4a5a-89c2-855a0634d5fe	Primary		Approved 8307	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

C_max

Value	Dose	Co-administered	Analyte	Population
20.57 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/022561Orig1s000ClinPharmR.pdf	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 REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/022561Orig1s000ClinPharmR.pdf	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

Value	Dose	Co-administered	Analyte	Population
69.4 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/022561Orig1s000ClinPharmR.pdf	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 REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/022561Orig1s000ClinPharmR.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
18.4 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/022561Orig1s000ClinPharmR.pdf	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 REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/022561Orig1s000ClinPharmR.pdf	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/24502830 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: https://pubmed.ncbi.nlm.nih.gov/24502830 Page: p.262	Disc. AE: Lymphopenia... AEs leading to discontinuation/dose reduction: Lymphopenia (grade 3-4) Sources: https://pubmed.ncbi.nlm.nih.gov/24502830 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: https://pubmed.ncbi.nlm.nih.gov/7911736 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: https://pubmed.ncbi.nlm.nih.gov/7911736 Page: p.170	DLT: Neutropenia, Leukopenia... Dose limiting toxicities: Neutropenia (grade 4, 50%) Leukopenia (grade 4, 50%) Sources: https://pubmed.ncbi.nlm.nih.gov/7911736 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: https://pubmed.ncbi.nlm.nih.gov/10720289 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: https://pubmed.ncbi.nlm.nih.gov/10720289 Page: p.1152	Sources: https://pubmed.ncbi.nlm.nih.gov/10720289 Page: p.1152

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/24502830 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: https://pubmed.ncbi.nlm.nih.gov/24502830 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: https://pubmed.ncbi.nlm.nih.gov/7911736 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: https://pubmed.ncbi.nlm.nih.gov/7911736 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: https://pubmed.ncbi.nlm.nih.gov/7911736 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: https://pubmed.ncbi.nlm.nih.gov/7911736 Page: p.170

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1670 inhibitor 1532 inducer 753	substrate 985 inhibitor 1695	substrate 1168 inhibitor 1789	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1463 CYP2B6 770 CYP2C8 869 CYP2C19 1410 CYP2E1 846 P-gp 1401 BCRP 678 MRP2 363 MRP4 202 MRP5 22 OATP1B1 770 OATP1B3 691 OAT1 584 OAT3 625 OAT4 145 OCT1 498 OCT2 630	CYP2E1 633 BCRP 545 P-gp 1491 MRP4 75 OCT2 336 OAT1 314 OAT3 328 OAT4 76 CYP1A2 1013 CYP2A6 510 CYP2C19 955	CYP1A2 671 CYP2B6 521

Drug as perpetrator

Target	Modality	Activity
BCRP 751	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP1A2 1620	inducer 1515 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP1A2 1620	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf	no
CYP2B6 946	inducer 1515 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP2B6 946	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf	no
CYP2C19 1484	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf	no
CYP2C8 923	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf	no
CYP2C9 1747	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf	no
CYP2D6 1826	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf	no
CYP2E1 929	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf	no
CYP3A4 1857	inducer 1515 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP3A4 1857	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf	no
MRP2 452	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
MRP4 235	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
MRP5 47	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OAT1 588	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OAT3 627	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OAT4 145	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OATP1B1 785	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OATP1B3 700	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OCT1 513	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OCT2 631	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
P-gp 1588	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no

Drug as victim

Target	Modality	Activity
CYP1A2 1013	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP2A6 510	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP2C19 955	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP2C9 985	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP2D6 1168	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP2E1 633	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP3A4 1670	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
MRP4 75	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OAT1 314	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OAT3 328	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OAT4 76	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OCT2 336	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
BCRP 545	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf \| https://pubmed.ncbi.nlm.nih.gov/18765824/	yes
P-gp 1491	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1603	inhibitor 1584 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:567361	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:567361
MolPort	MolPort-002-054-532	https://www.molport.com/shop/molecule-link/MolPort-002-054-532
Selleck Chemicals	Cladribine	http://www.selleckchem.com/products/Cladribine.html
ZINC	ZINC000003798064	http://zinc15.docking.org/substances/ZINC000003798064
eMolecules	29542740	https://www.emolecules.com/cgi-bin/more?vid=29542740

PubMed

Title	Date	PubMed
Severe skin rash in two consecutive patients treated with 2-chlorodeoxyadenosine for hairy cell leukaemia at a single institution.	2000 Apr	10792402
Guillain-Barre syndrome following 2-chlorodeoxyadenosine treatment for Hairy Cell Leukemia.	2000 Nov	11342351
[Nucleoside analogues--new drugs for the treatment of lymphatic cancers].	2001	12092367
[Lupus nephritis: treatments for today and tomorrow].	2001	11881420
Immunomodulatory drugs for multiple sclerosis: a systematic review of clinical and cost effectiveness.	2001 Apr	11336612
Langerhans cell histiocytosis: central nervous system involvement treated successfully with 2-chlorodeoxyadenosine.	2001 Apr-May	11293288
A phase II study of sequential combination chemotherapy with cyclophosphamide, prednisone, and 2-chlorodeoxyadenosine in previously untreated patients with chronic lymphocytic leukemia.	2001 Aug	11480558
Cladribine. Ortho Biotech Inc.	2001 Dec	11892941
Hematological effects of intermittent 2-hour infusions of cladribine in multiple sclerosis patients: a comparison of 2 dosage patterns.	2001 Dec	11794698
Second primary tumors and immune phenomena after fludarabine or 2-chloro-2'-deoxyadenosine treatment.	2001 Feb	11426527
Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation.	2001 Feb 1	11157478
Hairy cell leukemia.	2001 Jun	12057121
Nucleoside analogues: mechanisms of drug resistance and reversal strategies.	2001 Jun	11417472
Experience with 2-chlorodeoxyadenosine in previously untreated children with newly diagnosed acute myeloid leukemia and myelodysplastic diseases.	2001 Jun 1	11387351
Cladribine in combination with mitoxantrone and cyclophosphamide(CMC) in the treatment of heavily pre-treated patients with advanced indolent lymphoid malignancies.	2001 Mar	11350487
Effective treatment with rituximab in a patient with refractory prolymphocytoid transformed B-chronic lymphocytic leukemia and Evans syndrome.	2001 Mar	11320903
Immunosuppressive and cytotoxic drugs in the treatment of rheumatic skin disorders.	2001 Mar	11308138
Immunologic therapy for secondary and primary progressive multiple sclerosis.	2001 May	11898531
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	11872081
Efficacy of anti-CD20 monoclonal antibodies (Mabthera) in patients with progressed hairy cell leukemia.	2001 Oct	11602410
Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy in chronic lymphocytic leukemia.	2001 Oct	11587207
In vitro release of cytotoxic nucleoside analogs from lactide-caprolactone and lactide-glycolide copolymers.	2002	12136942
5'-Esters of 2'-deoxyadenosine and 2-chloro-2'-deoxyadenosine with cell differentiation-provoking agents.	2002	12136933
Therapeutic approaches in multiple sclerosis: lessons from failed and interrupted treatment trials.	2002	12102646
Immunosuppression with limited toxicity: the characteristics of nucleoside analogs and anti-lymphocyte antibodies used in non-myeloablative hematopoietic cell transplantation.	2002	11908199
Gateways to Clinical Trials.	2002 Apr	12087878
Simultaneous diagnosis of hairy cell leukemia and chronic lymphocytic leukemia/small lymphocytic lymphoma: a frequent association?	2002 Aug	12145685
Use of 2-chlorodeoxyadenosine to treat infantile myofibromatosis.	2002 Jan	11902743
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	12040435
Alkylating agents and nucleoside analogues in the treatment of B cell chronic lymphocytic leukemia.	2002 Jun	12040433
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	11849209
[Therapeutic effectiveness of cladribine and cellular immunodeficiency--related effects in hairy-cell leukemia?].	2002 May	12061204
Aggressive growth of epithelial carcinomas following treatment with nucleoside analogues.	2002 May	11994981
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	12110319

Patents

Sample Use Guides

In Vivo Use Guide

0.09 mg/kg/day

Route of Administration: Intravenous

In Vitro Use Guide

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

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Name

Type

Language

CLADRIBINE

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