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 8228
DNA 247 Target ID: CHEMBL2311221 Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=20634380	Binding Agent 1059
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 8228

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 8360	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 1709 inhibitor 1579 inducer 768	substrate 1010 inhibitor 1752	substrate 1193 inhibitor 1837	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2B6 799 CYP2C8 901 CYP2C19 1463 CYP2E1 876 P-gp 1437 BCRP 691 MRP2 367 MRP4 203 MRP5 22 OATP1B1 781 OATP1B3 700 OAT1 595 OAT3 636 OAT4 145 OCT1 506 OCT2 638	CYP2E1 648 BCRP 555 P-gp 1527 MRP4 75 OCT2 348 OAT1 320 OAT3 333 OAT4 76 CYP1A2 1032 CYP2A6 523 CYP2C19 985	CYP1A2 689 CYP2B6 538

Drug as perpetrator

Target	Modality	Activity
BCRP 765	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP1A2 1673	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP1A2 1673	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf	no
CYP2B6 985	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP2B6 985	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf	no
CYP2C19 1537	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf	no
CYP2C8 955	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf	no
CYP2C9 1803	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf	no
CYP2D6 1875	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf	no
CYP2E1 964	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf	no
CYP3A4 1909	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP3A4 1909	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf	no
MRP2 459	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
MRP4 237	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
MRP5 48	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OAT1 599	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OAT3 638	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OAT4 145	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OATP1B1 796	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OATP1B3 709	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OCT1 523	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OCT2 639	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
P-gp 1626	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no

Drug as victim

Target	Modality	Activity
CYP1A2 1032	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP2A6 523	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP2C19 985	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP2C9 1010	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP2D6 1193	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP2E1 648	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
CYP3A4 1709	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
MRP4 75	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OAT1 320	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OAT3 333	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OAT4 76	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
OCT2 348	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/	no
BCRP 555	substrate 3326 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 1527	substrate 3326 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 1632	inhibitor 1613 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
Immunomodulatory drugs for multiple sclerosis: a systematic review of clinical and cost effectiveness.	2001 Apr	11336612
Second primary tumors and immune phenomena after fludarabine or 2-chloro-2'-deoxyadenosine treatment.	2001 Feb	11426527
Purpuric rash following treatment with 2-chlorodeoxyadenosine.	2001 Feb	11422236
Candida tropicalis and Penicillium marneffei mixed fungaemia in a patient with Waldenström's macroglobulinaemia.	2001 Feb	11305468
Hairy cell leukemia.	2001 Jun	12057121
Immunosuppressive and cytotoxic drugs in the treatment of rheumatic skin disorders.	2001 Mar	11308138
Cladribine induces apoptosis in human leukaemia cells by caspase-dependent and -independent pathways acting on mitochondria.	2001 Nov 1	11672427
Efficacy of anti-CD20 monoclonal antibodies (Mabthera) in patients with progressed hairy cell leukemia.	2001 Oct	11602410
[Recent progress in the treatment of malignant lymphoma].	2001 Sep	11579632
In vitro release of cytotoxic nucleoside analogs from lactide-caprolactone and lactide-glycolide copolymers.	2002	12136942
Gateways to Clinical Trials.	2002 Apr	12087878
Radiation therapy and combination of cladribine, cyclophosphamide, and prednisone as treatment of Bing-Neel syndrome: Case report and review of the literature.	2002 Feb	11835349
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
Severe decrease in peripheral blood dendritic cells in hairy cell leukaemia.	2002 Mar	11849216
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

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 `Wed Jul 05 22:33:34 UTC 2023` Edited by `admin` on `Wed Jul 05 22:33:34 UTC 2023`
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