QuickView for Chlorambucil (compound)

Summary
General Info

PubChem

PubChem Compound 2708

Name:	Chlorambucil
PubChem Compound ID:	2708
Description:	A nitrogen mustard alkylating agent used as antineoplastic for chronic lymphocytic leukemia, Hodgkin's disease, and others. Although it is less toxic than most other nitrogen mustards, it has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (Merck Index, 11th ed)
Molecular formula:	C₁₄H₁₉Cl₂NO₂
Molecular weight:	304.212 g/mol
Synonyms:	Chlorbutin; Chloorambucol; 4-[Bis(2-chloroethyl)amino]benzenebutanoic acid; alkylating agent: crosslinks DNA; KBio2_000558; Chlorobutine; KBioSS_000558; p-(N,N-Di-2-chlorethylaminophenyl)butyric acid; 305-03-3; Benzenebutanoic acid, 4-[bis (2-chloroethyl)amino]-. show more » Chlorbutin; Chloorambucol; 4-[Bis(2-chloroethyl)amino]benzenebutanoic acid; alkylating agent: crosslinks DNA; KBio2_000558; Chlorobutine; KBioSS_000558; p-(N,N-Di-2-chlorethylaminophenyl)butyric acid; 305-03-3; Benzenebutanoic acid, 4-[bis (2-chloroethyl)amino]-; Kyselina 4-(N,N-bis-(2-chlorethyl)-p-aminofenyl)maselna [Czech]; Chlorambucilum [INN-Latin]; N,N-Di-2-chloroethyl-gamma-para-aminophenyl butyric acid; Chloraminophene; NCGC00023250-03; Linfolizin; Chlorbutinum; Lympholysin; Clorambucilo [INN-Spanish]; AI3-26083; SPBio_002999; Leukersan; gamma-[p-di(2-chloroethyl)aminophenyl]butyric acid; 4-(Bis(2-chloroethyl)amino)phenylbutyric acid; KBio2_005694; KBio3_001191; .gamma.-[p-Di(2-chloroethyl)aminophenyl]butyric acid; Leukeran (TN); Chlorobutin; 4[p-Bis(.beta.-chloroethyl)aminophenyl]butyric acid; chloraminophen; Prestwick0_001079; p-N, N-Di-(.beta.-chloroethyl)aminophenyl butyric acid; RCRA waste no. U035; NSC-3088; Spectrum3_000336; KBio2_003126; Clorambucile [DCIT]; AIDS-026810; RCRA waste number U035; NINDS_000688; CAS-305-03-3; Leukeran; 4-{4-[bis(2-chloroethyl)amino]phenyl}butanoic acid; CHEBI:28830; p-(N,N-Di-2-chloroethyl)aminophenyl butyric acid; 4-[p-[bis(2-chloroethyl)amino]phenyl]butyric acid; Ambochlorin; p-(N, N-Di-2-chloroethyl)aminophenyl butyric acid; D00266; Chlorbutine; NCGC00015199-02; 4-(p-bis(beta-chloroethyl)aminophenyl)butyric acid; NCGC00015199-01; CCRIS 126; 4-[Bis(2-chloroethyl)amino]phenylbutyric acid; Cb l348; gamma-(p-bis(2-chloroethyl)aminophenyl)butyricacid; Lopac-C-0253; Linfolysin; DivK1c_000688; Benzenebutanoic acid, 4-[bis(2-chloroethyl)amino]-; MLS000028443; BRN 0999011; .gamma.-[p-bis(2-chloroethyl)aminophenyl]butyric acid; Butyric acid, 4-(p-bis(2-chloroethyl)aminophenyl)-; Ecloril; para-(Di(2-chloroethyl)aminophenyl)butyric acid; 4-[p-Bis(.beta.-chloroethyl)aminophenyl]butyric acid; SPBio_000249; SMR000058372; 4-14-00-01715 (Beilstein Handbook Reference); Butyric acid, 4-(p-[bis(2-chloroethyl)amino]phenyl)-; N,N-Di-2-chloroethyl-.gamma.-p-aminophenylbutyric acid; NSC3088; NCI-C03485; NSC 3088; Benzenebutanoic acid, 4-(bis(2-chloroethyl)amino)-; gamma-(p-Bis(2-chloroethyl)aminophenyl)butyric acid; NCI60_002639; EINECS 206-162-0; N,N-di-2-chloroethyl-gamma-p-aminophenylbutyric acid; .gamma.-(p-bis(2-chloroethyl)aminophenyl)butyric acid; HSDB 3026; AIDS026810; KBioGR_000766; Butyric acid, 4-(p-(bis(2-chloroethyl)amino)phenyl); Butanoic acid, 4-(bis(2-chloroethyl)amino) benzene; gamma-(p-Di(2-chloroethyl)aminophenyl)butyric acid; Elcoril; Elcorin; Prestwick1_001079; 4-(Bis(2-chloroethyl)amino)benzenebutanoic acid; Phenylbuttersaeure-lost [German]; p-N,N-Di-(beta-chloroethyl)aminophenyl butyric acid; Chlorambucil (USP); Cbl; Chlorambucil; Leukoran; Spectrum2_000065; Chlorambucil [BAN:INN]; Butyric acid, 4-[p-[bis (2-chloroethyl)amino]phenyl]-; phenylbutyric acid nitrogen mustard; EU-0100227; Spectrum_000118; Spectrum4_000273; KBio1_000688; para-N,N-Di(beta-chloroethyl)aminophenyl butyric acid; Amboclorin; 4-(p-(Bis(2-chloroethyl)amino)phenyl)butyric acid; CB 1348; Chloroambucil show less «

DrugBank

Identification

Name:	Chlorambucil
Name (isomeric):	DB00291
Drug Type:	small molecule
Description:	A nitrogen mustard alkylating agent used as antineoplastic for chronic lymphocytic leukemia, Hodgkin's disease, and others. Although it is less toxic than most other nitrogen mustards, it has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (Merck Index, 11th ed)
Synonyms:	Chloraminophene; Chlorbutin; Chlorbutine; Chlocambucil; Chloraminophen; Phenylbutyric Acid Nitrogen Mustard; Chlorobutine; Chloroambucil; Chlorobutin
Brand:	Linfolysin, Ambochlorin, Pepstatin, Elcoril, Ecloril, Leukeran, Linfolizin, Leukoran, Leukeran Tablets, Leukersan, Amboclorin
Category:	Antineoplastic Agents, Antineoplastic Agents, Alkylating
CAS number:	305-03-3

Pharmacology

Indication:	For treatment of chronic lymphatic (lymphocytic) leukemia, childhood minimal-change nephrotic syndrome, and malignant lymphomas including lymphosarcoma, giant follicular lymphoma, Hodgkin's disease, non-Hodgkin's lymphomas, and Waldenström’s Macroglobulinemia.
Pharmacology:	Chlorambucil is an antineoplastic in the class of alkylating agents that is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly ... show more » Chlorambucil is an antineoplastic in the class of alkylating agents that is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death. show less «
Mechanism of Action:	Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the D... show more » Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations. show less «
Protein binding:	99%
Route of elimination:	Chlorambucil is extensively metabolized in the liver primarily to phenylacetic acid mustard. The pharmacokinetic data suggests that oral chlorambucil undergoes rapid gastrointestinal absorption and plasma clearance and that it is almost completely metabolized, having extremely low urinary excretion.
Half Life:	1.5 hours
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Drink liberally.

Echinacea should be used with caution, if at all, in patients receiving therapeutic immunosuppressants. Monitor for reduced efficacy of the immunosuppressant during concomitant use.

Take on an empty stomach.

Food reduces bioavailability.

Drug interaction:

Tacrolimus	Tacrolimus (Topical) may enhance the adverse/toxic effect of immunosuppressants sucb as chlorambucil. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.
Roflumilast	Roflumilast may enhance the immunosuppressive effect of immunosuppressants such as chlorambucil. The Canadian roflumilast product monograph recommends avoiding concurrent use of roflumilast with any immunosuppressant medications due to the antiinflammatory/immune altering effects of roflumilast and the lack of relevant clinical experience with such use. Of note, this recommendation to avoid concurrent use does not apply to either inhaled corticosteroids (which have much more limited systemic immune-suppressing actions) or short-term systemic corticosteroid use. U.S. prescribing information does not contain this warning; but it appears prudent to avoid this combination when possible.
Natalizumab	Immunosuppressants such as chlorambucil may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.
Trastuzumab	Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Pimecrolimus	Pimecrolimus may enhance the adverse/toxic effect of immunosuppressants such as chlorambucil. Avoid use of pimecrolimus cream in patients receiving immunosuppressants.

Tacrolimus	Tacrolimus (Topical) may enhance the adverse/toxic effect of immunosuppressants sucb as chlorambucil. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.
Roflumilast	Roflumilast may enhance the immunosuppressive effect of immunosuppressants such as chlorambucil. The Canadian roflumilast product monograph recommends avoiding concurrent use of roflumilast with any immunosuppressant medications due to the antiinflammatory/immune altering effects of roflumilast and the lack of relevant clinical experience with such use. Of note, this recommendation to avoid concurrent use does not apply to either inhaled corticosteroids (which have much more limited systemic immune-suppressing actions) or short-term systemic corticosteroid use. U.S. prescribing information does not contain this warning; but it appears prudent to avoid this combination when possible.
Natalizumab	Immunosuppressants such as chlorambucil may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.
Trastuzumab	Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Pimecrolimus	Pimecrolimus may enhance the adverse/toxic effect of immunosuppressants such as chlorambucil. Avoid use of pimecrolimus cream in patients receiving immunosuppressants.
Leflunomide	Immunosuppressants such as chlorambucil may enhance the adverse/toxic effect of leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Consider eliminating the use of a leflunomide loading dose in patients who are receiving other immunosuppressants in order to reduce the risk for serious adverse events such as hematologic toxicity. Also, patients receiving both leflunomide and another immunosuppressive medication should be monitored for bone marrow suppression at least monthly throughout the duration of concurrent therapy.

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Targets

DNA

Enzymes

Glutathione S-transferase P