CHLORAMBUCIL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H19Cl2NO2
Molecular Weight	304.212
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CCCC1=CC=C(C=C1)N(CCCl)CCCl

InChI

InChIKey=JCKYGMPEJWAADB-UHFFFAOYSA-N

InChI=1S/C14H19Cl2NO2/c15-8-10-17(11-9-16)13-6-4-12(5-7-13)2-1-3-14(18)19/h4-7H,1-3,8-11H2,(H,18,19)

HIDE SMILES / InChI

Molecular Formula	C14H19Cl2NO2
Molecular Weight	304.212
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/010669s032lbl.pdf

Chlorambucil is a bifunctional 12 alkylating agent of the nitrogen mustard type that has been found active against selected human 13 neoplastic diseases. Chlorambucil alkylates and cross-links DNA during all phases of the cell cycle, inducing DNA damage via three different methods of covalent adduct generation with double-helical DNA. Bone marrow suppression (anemia, neutropenia, thrombocytopenia) is the most commonly occurring side effect of chlorambucil. There are no known drug/drug interactions with chlorambucil.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 247 Target ID: CHEMBL2311221 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/010669s032lbl.pdf	Crosslinking Agent 80

Conditions

Condition	Modality	Highest Phase	Product
Giant follicular lymphoma 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/010669s032lbl.pdf	Primary	Approved 8360	LEUKERAN Approved Use LEUKERAN (chlorambucil) is indicated in the treatment of chronic lymphatic (lymphocytic) leukemia, malignant lymphomas including lymphosarcoma, giant follicular lymphoma, and Hodgkin’s disease. It is not curative in any of these disorders but may produce clinically useful palliation. Launch Date -4.036608E11
Hodgkin's lymphoma 34 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/010669s032lbl.pdf	Primary	Approved 8360	LEUKERAN Approved Use LEUKERAN (chlorambucil) is indicated in the treatment of chronic lymphatic (lymphocytic) leukemia, malignant lymphomas including lymphosarcoma, giant follicular lymphoma, and Hodgkin’s disease. It is not curative in any of these disorders but may produce clinically useful palliation. Launch Date -4.036608E11
Chronic lymphocytic leukemia 59 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/010669s032lbl.pdf	Primary	Approved 8360	LEUKERAN Approved Use LEUKERAN (chlorambucil) is indicated in the treatment of chronic lymphatic (lymphocytic) leukemia, malignant lymphomas including lymphosarcoma, giant follicular lymphoma, and Hodgkin’s disease. It is not curative in any of these disorders but may produce clinically useful palliation. Launch Date -4.036608E11
Lymphosarcoma 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/010669s032lbl.pdf	Primary	Approved 8360	LEUKERAN Approved Use LEUKERAN (chlorambucil) is indicated in the treatment of chronic lymphatic (lymphocytic) leukemia, malignant lymphomas including lymphosarcoma, giant follicular lymphoma, and Hodgkin’s disease. It is not curative in any of these disorders but may produce clinically useful palliation. Launch Date -4.036608E11

C_max

Value	Dose	Co-administered	Analyte	Population
1.46 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/6489421	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORAMBUCIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
259 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/6840176	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORAMBUCIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
1.99 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/6489421	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORAMBUCIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
380 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/6840176	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORAMBUCIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.94 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/6489421	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORAMBUCIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/967ed3ff-d99b-41e8-b768-dfb586d3d9a6/spl-doc?hl=chlorambucil			CHLORAMBUCIL plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
3.2 mg/kg single, oral Overdose Dose: 3.2 mg/kg Route: oral Route: single Dose: 3.2 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/3065402	healthy, 1.8 n = 1 Health Status: healthy Age Group: 1.8 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/3065402	Disc. AE: Irritability, Myoclonic jerks... AEs leading to discontinuation/dose reduction: Irritability Myoclonic jerks Exaggerated startle response Vomiting Bone marrow depression (mild) Abnormal EEG Sources: https://pubmed.ncbi.nlm.nih.gov/3065402
5 mg/kg single, oral Overdose Dose: 5 mg/kg Route: oral Route: single Dose: 5 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/13462782 Page: p.239	healthy, 2.5 n = 1 Health Status: healthy Age Group: 2.5 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/13462782 Page: p.239	Disc. AE: Convulsive seizure, Comatose... AEs leading to discontinuation/dose reduction: Convulsive seizure Comatose Vomiting Sources: https://pubmed.ncbi.nlm.nih.gov/13462782 Page: p.239
250 mg single, oral Overdose Dose: 250 mg Route: oral Route: single Dose: 250 mg Co-administed with:: cimetidine, p.o(600 mg; single) aspirin Sources: https://pubmed.ncbi.nlm.nih.gov/6655776	healthy, 38 n = 1 Health Status: healthy Age Group: 38 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6655776	Disc. AE: Acute renal failure, Seizures... AEs leading to discontinuation/dose reduction: Acute renal failure Seizures Sources: https://pubmed.ncbi.nlm.nih.gov/6655776
0.2 mg/kg 1 times / day multiple, oral (max) Recommended Dose: 0.2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 0.2 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/010669s032lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Chronic lymphatic leukemia\|Malignant lymphomas Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/010669s032lbl.pdf Page: p.1	Disc. AE: Bone marrow depression, Carcinogenicity... AEs leading to discontinuation/dose reduction: Bone marrow depression Carcinogenicity Infertility Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/010669s032lbl.pdf Page: p.1
0.2 mg/kg 1 times / day multiple, oral (max) Recommended Dose: 0.2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 0.2 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/010669s032lbl.pdf Page: p.2	unhealthy Health Status: unhealthy Condition: Chronic lymphatic leukemia\|Malignant lymphomas Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/010669s032lbl.pdf Page: p.2	Disc. AE: Convulsions, Metastases... AEs leading to discontinuation/dose reduction: Convulsions Metastases Leukemia Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/010669s032lbl.pdf Page: p.2
0.2 mg/kg 1 times / day multiple, oral (max) Recommended Dose: 0.2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 0.2 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/010669s032lbl.pdf Page: p.3	unhealthy Health Status: unhealthy Condition: Chronic lymphatic leukemia\|Malignant lymphomas Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/010669s032lbl.pdf Page: p.3	Disc. AE: Skin rash, Erythema multiforme... AEs leading to discontinuation/dose reduction: Skin rash (rare) Erythema multiforme (rare) Toxic epidermal necrolysis (rare) Stevens-Johnson syndrome (rare) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/010669s032lbl.pdf Page: p.3

AEs

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:28830	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:28830
ChemicalBook	CB5270716	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5270716
MolPort	MolPort-000-152-694	https://www.molport.com/shop/molecule-link/MolPort-000-152-694
ZINC	ZINC000000001115	http://zinc15.docking.org/substances/ZINC000000001115
eMolecules	490279	https://www.emolecules.com/cgi-bin/more?vid=490279

PubMed

Title	Date	PubMed
Treatment of membranous nephropathy.	2001	11509678
[Treatment of uveitis with immunosuppressives: antimetabolites and alkylating agents].	2001	11344715
Severe bone marrow failure associated with the use of alternating steroid with chlorambucil in lupus membranous nephropathy in Chinese.	2001	11341107
Esters of chlorambucil with 2-substituted 1,4-dihydroxy-9,10-anthraquinones as multifunctional anticancer agents.	2001 Apr	11461761
Decreased cytotoxicity and increased antimitotic activity of a proline analogue of chlorambucil as a prodrug susceptible to the action of fibroblast's prolidase.	2001 Apr	11338665
[Renal involvement in Waldenstroms macroglobulinemia. Case report and review of the literature].	2001 Apr	11323576
Treatment of Behçet's disease--an update.	2001 Apr	11303303
DNA minor groove alkylating agents.	2001 Apr	11281840
Fludarabine for chronic lymphocytic leukemia.	2001 Apr 12	11302141
Fludarabine for chronic lymphocytic leukemia.	2001 Apr 12	11302140
Reactions of N,N-bis(2-chloroethyl)-p-aminophenylbutyric acid (chlorambucil) with 2'-deoxyguanosine.	2001 Aug	11511172
Stage I and II MALT lymphoma: results of treatment with radiotherapy.	2001 Aug 1	11483337
Impact of therapy With chlorambucil, fludarabine, or fludarabine plus chlorambucil on infections in patients with chronic lymphocytic leukemia: Intergroup Study Cancer and Leukemia Group B 9011.	2001 Aug 15	11504743
Waldenström's macroglobulinemia: clinical course and prognostic factors in 60 patients. Experience from a single hematology unit.	2001 Dec	11797112
Screening for inhibitory effects of antineoplastic agents on CYP3A4 in human liver microsomes.	2001 Dec	11770832
The Chinese hamster FANCG/XRCC9 mutant NM3 fails to express the monoubiquitinated form of the FANCD2 protein, is hypersensitive to a range of DNA damaging agents and exhibits a normal level of spontaneous sister chromatid exchange.	2001 Dec	11751423
Waldenström macroglobulinaemia: presenting features and outcome in a series with 217 cases.	2001 Dec	11736938
[Bendamustine, vincristine, prednisolone (BOP) in therapy of advanced low-grade non-Hodgkin lymphoma]].	2001 Feb 23	11256023
New aspects on the pathogenesis, diagnostic procedures, and therapeutic management of chronic lymphocytic leukemia.	2001 Jan	11372752
[Usefulness of the blink reflex in a case of brainstem neuro-Behcet's disease].	2001 Jan 1-15	11293105
Granulomatous slack skin: a distinct disorder or a variant of mycosis fungoides?	2001 Jan-Feb	11411914
Cutaneous xanthomas with concurrent demodicosis and dermatophytosis in a cat.	2001 Jul	11549045
Genetic damage by bifunctional agents in repair-active pre-meiotic stages of Drosophila males.	2001 Jul 1	11406175
UCN-01 induces cytotoxicity toward human CLL cells through a p53-independent mechanism.	2001 Jun	11378265
Chlorambucil/prednisone-induced seizures in a patient with non-Hodgkin's lymphoma.	2001 Jun	11343390
The cell transmembrane pH gradient in tumors enhances cytotoxicity of specific weak acid chemotherapeutics.	2001 Jun 15	11406545
[Chronic lymphatic leukemia. 3. The concrete case].	2001 Jun 8	11464816
Acquired Factor VIII autoantibody: four cases demonstrating the heterogenous nature of this condition and problems involved in diagnosis and treatment.	2001 Mar	11350490
Immunosuppressive and cytotoxic drugs in the treatment of rheumatic skin disorders.	2001 Mar	11308138
Primary low-grade B cell non-Hodgkin's lymphoma of MALT type simultaneously arising in the colon and in the lung: report of a case.	2001 Mar	11289295
Use of methotrexate in the management of sight-threatening uveitis.	2001 Mar	11262666
Lung cancer after Hodgkin's disease: a nested case-control study of the relation to treatment.	2001 Mar 15	11250989
Synthesis and antitumor activity of novel paclitaxel-chlorambucil hybrids.	2001 Mar 26	11277526
Hypercalcaemia associated with chronic lymphocytic leukaemia in a Giant Schnauzer.	2001 May	11431998
Does intensive treatment with high dose chlorambucil and prednisone as first line and cladribine as second line influence the survival of the patients with chronic lymphocytic leukemia?	2001 May	11378572
Treatment of myelopathy in Sjögren syndrome with a combination of prednisone and cyclophosphamide.	2001 May	11346378
Induction of mutant lymphocytes in cyclophosphamide- and chlorambucil-treated patients.	2001 May	11320143
Novel treatment strategies in chronic lymphocytic leukemia.	2001 May	11296131
[Pneumonia in patients with chronic lymphocytic leukemia. Study of 30 episodes].	2001 May 26	11412696
2-[N1-2-pyrimidyl-aminobenzenesulfonamido] ethyl 4-bis(2-chloroethyl) aminophenyl butyrate: a potent antitumor agent.	2001 May 7	11354353
Giant cell arteritis and renal amyloidosis: report of a case.	2001 Nov	11758014
Prediction of subsequent relapse in children with steroid-sensitive nephrotic syndrome.	2001 Nov	11685595
Blastic variant of mantle cell lymphoma: a rare but highly aggressive subtype.	2001 Nov	11681422
Caspase 8 activation independent of Fas (CD95/APO-1) signaling may mediate killing of B-chronic lymphocytic leukemia cells by cytotoxic drugs or gamma radiation.	2001 Nov 1	11675354
Lymphoplasmacytic lymphoma/immunocytoma: towards a disease-targeted treatment?	2001 Sep	11718214
[Vascular purpura in a patient with severe sarcoptic acariasis].	2001 Sep	11590343
Autologous plasma activates Akt/protein kinase B and enhances basal survival and resistance to DNA damage-induced apoptosis in B-chronic lymphocytic leukaemia cells.	2001 Sep	11552986
Induction of apoptosis by the ADEPT agent ZD2767: comparison with the classical nitrogen mustard chlorambucil and a monofunctional ZD2767 analogue.	2001 Sep 1	11531265
Cutaneous necrobiotic xanthogranuloma (NXG)--successfully treated with low dose chlorambucil.	2001 Sep-Oct	11525957
Efficacy and safety of chlorambucil in intractable noninfectious uveitis: the Massachusetts Eye and Ear Infirmary experience.	2002 Jan	11772593

Patents

Sample Use Guides

In Vivo Use Guide

0.1 to 0.2 mg/kg body weight daily for 3 to 6 weeks

Route of Administration: Oral

In Vitro Use Guide

The inhibition of 3H-thymidine incorporation into the DNA of mitogen-stimulated lymphocytes from patients with chronic lymphocytic leukaemia by chlorambucil was measured in vitro. For the lymphocytes from the untreated patients the mean ID50 was 3.1 ug/ml.

Substance Class	Chemical Created by `admin` on `Wed Jul 05 22:30:30 UTC 2023` Edited by `admin` on `Wed Jul 05 22:30:30 UTC 2023`
Record UNII	18D0SL7309
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CHLORAMBUCIL

Official Name

English

CB-1348

Code

English

CHLORAMBUCIL [JAN]

Common Name

English

CHLORAMBUCIL [EP MONOGRAPH]

Common Name

English

CHLORAMBUCIL [IARC]

Common Name

English

4-(P-(BIS(2-CHLOROETHYL)AMINO)PHENYL)BUTYRIC ACID

Common Name

English

CHLORAMBUCILUM [WHO-IP LATIN]

Common Name

English

Chlorambucil [WHO-DD]

Common Name

English

AMBOCHLORIN

Common Name

English

LEUKERAN

Brand Name

English

NSC-3088

Code

English

CHLORAMBUCIL [VANDF]

Common Name

English

ECLORIL

Common Name

English

BENZENEBUTANOIC ACID, 4-(BIS(2-CHLOROETHYL)AMINO)-

Common Name

English

LYMPHOLYSIN

Common Name

English

CHLORAMBUCIL [MART.]

Common Name

English

CHLORAMBUCIL [HSDB]

Common Name

English

CHLORAMBUCIL [WHO-IP]

Common Name

English

NCI-3088

Code

English

CHLORAMBUCIL [USP-RS]

Common Name

English

chlorambucil [INN]

Common Name

English

CHLORAMBUCIL [ORANGE BOOK]

Common Name

English

CHLORAMBUCIL [MI]

Common Name

English

CHLORAMBUCIL [USP MONOGRAPH]

Common Name

English

Classification Tree Code System Code

LIVERTOX

NBK548207