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chlorambucil 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
	588	305-03-3

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: chlorambucil ambochlorin amboclorin chloraminophene chlorbutin chlorobutine	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 weight: 304.21 Formula: C14H19Cl2NO2 CLOGP: 3.63 LIPINSKI: 0 HAC: 3 HDO: 1 TPSA: 40.54 ALOGS: -3.59 ROTB: 9 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

chlorambucil
ambochlorin
amboclorin
chloraminophene
chlorbutin
chlorobutine

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 weight: 304.21
Formula: C14H19Cl2NO2
CLOGP: 3.63
LIPINSKI: 0
HAC: 3
HDO: 1
TPSA: 40.54
ALOGS: -3.59
ROTB: 9

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

None

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	0.09 mg/mL	Bocci G, Oprea TI, Benet LZ
EoM (Fraction excreted unchanged in urine)	0.50 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.66 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	82 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	0.26 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	2.80 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.01 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	1.10 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
March 18, 1957	FDA	ASPEN GLOBAL INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Progressive multifocal leukoencephalopathy	126.56	27.08	37	2186	12934	63473865
Neutropenia	97.82	27.08	66	2157	174939	63311860
Hypogammaglobulinaemia	81.32	27.08	23	2200	7132	63479667
Campylobacter infection	63.04	27.08	13	2210	1063	63485736
Febrile neutropenia	52.83	27.08	39	2184	118410	63368389
Thrombocytopenia	52.70	27.08	43	2180	151114	63335685
Myelodysplastic syndrome	51.25	27.08	20	2203	16734	63470065
Neutropenic infection	48.89	27.08	11	2212	1356	63485443
Disease progression	47.19	27.08	37	2186	122721	63364078
Encephalitis viral	46.30	27.08	11	2212	1721	63485078
Chronic lymphocytic leukaemia	41.80	27.08	11	2212	2603	63484196
Anaemia	33.52	27.08	46	2177	293384	63193415
Chronic lymphocytic leukaemia recurrent	33.34	27.08	6	2217	238	63486561
Off label use	32.41	27.08	72	2151	674390	62812409
Pyrexia	31.87	27.08	58	2165	470420	63016379
Blood disorder	31.47	27.08	11	2212	6760	63480039
Lymphopenia	29.84	27.08	14	2209	18313	63468486
Tumour lysis syndrome	28.43	27.08	11	2212	8979	63477820
Diffuse large B-cell lymphoma	27.76	27.08	10	2213	6702	63480097

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Acute myeloid leukaemia	207.55	24.15	81	4486	18189	34934175
Myositis	167.62	24.15	62	4505	12008	34940356
Microsporidia infection	149.54	24.15	31	4536	675	34951689
Progressive multifocal leukoencephalopathy	116.83	24.15	45	4522	9719	34942645
Second primary malignancy	103.90	24.15	39	4528	7847	34944517
Pneumonia	94.96	24.15	169	4398	362458	34589906
Myelodysplastic syndrome	87.61	24.15	45	4522	19163	34933201
Malignant transformation	84.00	24.15	20	4547	831	34951533
Neutropenia	79.74	24.15	100	4467	156678	34795686
Cerebral aspergillosis	73.67	24.15	20	4547	1412	34950952
Polymyositis	73.38	24.15	20	4547	1433	34950931
T-cell lymphoma stage IV	65.53	24.15	12	4555	132	34952232
Tumour lysis syndrome	60.99	24.15	34	4533	17025	34935339
Transformation to acute myeloid leukaemia	60.12	24.15	15	4552	759	34951605
Neutropenic sepsis	53.51	24.15	29	4538	13738	34938626
Chronic lymphocytic leukaemia recurrent	53.01	24.15	12	4555	398	34951966
Blood stem cell transplant failure	52.67	24.15	12	4555	410	34951954
Thrombocytopenia	51.46	24.15	81	4486	156166	34796198
Infusion related reaction	50.07	24.15	47	4520	53010	34899354
Hypogammaglobulinaemia	46.82	24.15	22	4545	7718	34944646
Enterococcal infection	45.89	24.15	23	4544	9283	34943081
Procalcitonin increased	43.85	24.15	14	4553	1737	34950627
Febrile neutropenia	39.66	24.15	67	4500	136782	34815582
Lymphopenia	38.71	24.15	25	4542	16310	34936054
Malignant neoplasm progression	38.13	24.15	52	4515	87994	34864370
Chronic lymphocytic leukaemia refractory	37.51	24.15	7	4560	86	34952278
Pyrexia	36.03	24.15	110	4457	332903	34619461
Bone marrow failure	35.71	24.15	30	4537	29223	34923141
Pseudomonas infection	34.49	24.15	21	4546	12361	34940003
Respiratory tract infection	34.45	24.15	25	4542	19687	34932677
Treatment failure	32.34	24.15	35	4532	46662	34905702
Device related infection	30.44	24.15	22	4545	17215	34935149
Genotoxicity	29.20	24.15	5	4562	36	34952328
Central nervous system lymphoma	28.99	24.15	9	4558	1019	34951345
Autoimmune haemolytic anaemia	27.87	24.15	13	4554	4483	34947881
Septic shock	27.48	24.15	40	4527	71794	34880570
Lymphadenopathy	26.41	24.15	25	4542	28438	34923926
Disease progression	26.22	24.15	49	4518	108028	34844336
Campylobacter infection	25.64	24.15	8	4559	921	34951443
Diffuse large B-cell lymphoma	24.46	24.15	14	4553	7356	34945008

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Progressive multifocal leukoencephalopathy	214.28	23.62	74	5908	20526	79717880
Acute myeloid leukaemia	202.62	23.62	79	5903	30806	79707600
Myositis	173.11	23.62	62	5920	19106	79719300
Microsporidia infection	156.97	23.62	31	5951	935	79737471
Neutropenia	152.15	23.62	144	5838	287566	79450840
Myelodysplastic syndrome	122.75	23.62	55	5927	30246	79708160
Hypogammaglobulinaemia	109.81	23.62	40	5942	12911	79725495
Second primary malignancy	109.45	23.62	41	5941	14309	79724097
Tumour lysis syndrome	89.18	23.62	41	5941	23898	79714508
Pneumonia	89.16	23.62	169	5813	660077	79078329
Thrombocytopenia	85.17	23.62	102	5880	265157	79473249
Malignant transformation	82.53	23.62	19	5963	1199	79737207
Cerebral aspergillosis	80.17	23.62	20	5962	1776	79736630
Campylobacter infection	79.45	23.62	20	5962	1843	79736563
T-cell lymphoma stage IV	71.45	23.62	12	5970	141	79738265
Polymyositis	69.77	23.62	20	5962	3016	79735390
Febrile neutropenia	66.29	23.62	84	5898	230915	79507491
Chronic lymphocytic leukaemia recurrent	65.35	23.62	14	5968	634	79737772
Lymphopenia	62.79	23.62	35	5947	30522	79707884
Malignant neoplasm progression	60.31	23.62	62	5920	135928	79602478
Disease progression	57.61	23.62	70	5912	184292	79554114
Neutropenic sepsis	55.60	23.62	31	5951	27033	79711373
Pyrexia	54.23	23.62	141	5841	678568	79059838
Procalcitonin increased	48.21	23.62	15	5967	2991	79735415
Enterococcal infection	46.63	23.62	23	5959	15637	79722769
Diffuse large B-cell lymphoma	42.71	23.62	20	5962	12129	79726277
Neutropenic infection	42.69	23.62	13	5969	2414	79735992
Respiratory tract infection	41.17	23.62	32	5950	48657	79689749
Cytopenia	40.92	23.62	23	5959	20360	79718046
Blood stem cell transplant failure	39.76	23.62	9	5973	526	79737880
Chronic lymphocytic leukaemia refractory	39.27	23.62	7	5975	119	79738287
Transformation to acute myeloid leukaemia	39.04	23.62	10	5972	987	79737419
Chronic lymphocytic leukaemia	37.44	23.62	14	5968	4852	79733554
Infusion related reaction	37.29	23.62	64	5918	230173	79508233
JC virus infection	36.69	23.62	13	5969	3868	79734538
Pseudomonas infection	35.09	23.62	21	5961	20882	79717524
Septic shock	34.12	23.62	44	5938	122757	79615649
Bone marrow failure	33.57	23.62	29	5953	51078	79687328
Anaemia	32.91	23.62	90	5892	444925	79293481
Off label use	31.71	23.62	143	5839	907072	78831334
Chills	30.59	23.62	48	5934	160186	79578220
Device related infection	29.99	23.62	23	5959	34271	79704135
Squamous cell carcinoma	29.66	23.62	17	5965	15605	79722801
Encephalitis viral	29.65	23.62	10	5972	2569	79735837
Blood disorder	27.18	23.62	13	5969	8260	79730146
Central nervous system lymphoma	26.81	23.62	9	5973	2280	79736126
Lymphadenopathy	26.74	23.62	26	5956	53221	79685185
Prostatic abscess	25.70	23.62	6	5976	402	79738004
Dermatitis exfoliative generalised	25.70	23.62	12	5970	7229	79731177
Blood pressure decreased	25.09	23.62	34	5948	99432	79638974
Panniculitis	24.94	23.62	14	5968	12357	79726049
Pain	24.69	23.62	11	5971	703791	79034615
Hepatitis B surface antigen positive	24.62	23.62	5	5977	174	79738232
Peripheral T-cell lymphoma unspecified stage IV	24.40	23.62	4	5978	40	79738366
Cytomegalovirus infection	23.65	23.62	22	5960	42622	79695784

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01AA02	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS ALKYLATING AGENTS Nitrogen mustard analogues
FDA MoA	N0000000236	Alkylating Activity
FDA EPC	N0000175558	Alkylating Drug
MeSH PA	D000477	Alkylating Agents
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D018906	Antineoplastic Agents, Alkylating
MeSH PA	D009676	Noxae
CHEBI has role	CHEBI:35610	antineoplastic agents
CHEBI has role	CHEBI:35705	immunosuppressive agents
CHEBI has role	CHEBI:50903	carcinogen
CHEBI has role	CHEBI:88188	allergenic drug

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Chronic lymphoid leukemia, disease	indication	92814006
Hodgkin's disease	indication	118599009
Follicular non-Hodgkin's lymphoma	indication	308121000
Minimal change disease	off-label use	44785005	DOID:10966
Mycosis fungoides	off-label use	118618005
Waldenström macroglobulinemia	off-label use	190818004	DOID:0050747
Primary cutaneous T-cell lymphoma	off-label use	400122007
Lowered convulsive threshold	contraindication	19260006
Lymphocytopenia	contraindication	48813009	DOID:614
Fibrosis of lung	contraindication	51615001	DOID:3770
Nephrotic syndrome	contraindication	52254009	DOID:1184
Acute infectious disease	contraindication	63171007
Interstitial pneumonia	contraindication	64667001
Leukopenia	contraindication	84828003	DOID:615
Acute leukemia, disease	contraindication	91855006	DOID:12603
Secondary malignant neoplasm of bone marrow	contraindication	94217008
Radiation oncology AND/OR radiotherapy	contraindication	108290001
Seizure disorder	contraindication	128613002
Drug-induced hepatitis	contraindication	235876009
Anemia	contraindication	271737000	DOID:2355
Pregnancy, function	contraindication	289908002
Thrombocytopenic disorder	contraindication	302215000	DOID:1588
Neutropenic disorder	contraindication	303011007	DOID:1227
Bone marrow depression	contraindication	307762000
Breastfeeding (mother)	contraindication	413712001

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	4.65	acidic
pKa2	3.71	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Type	Activity value (-log[M])	Bioact source
Delta-type opioid receptor	GPCR	P41143	OPRD_HUMAN	IC50	5.55	WOMBAT-PK
Cathepsin D	Enzyme	P07339	CATD_HUMAN	IC50	8.93	WOMBAT-PK
Cathepsin E	Enzyme	P14091	CATE_HUMAN	IC50	8.78	WOMBAT-PK
Disintegrin and metalloproteinase domain-containing protein 9	Enzyme	Q13443	ADAM9_HUMAN	IC50	7.25	WOMBAT-PK
Aldose reductase	Enzyme		ALDR_RAT	IC50	5.03	DRUG MATRIX

External reference:

ID	Source
4018769	VUID
N0000147072	NUI
D00266	KEGG_DRUG
2346	RXNORM
C0008163	UMLSCUI
CHEBI:28830	CHEBI
CBL	PDB_CHEM_ID
CHEMBL515	ChEMBL_ID
DB00291	DRUGBANK_ID
D002699	MESH_DESCRIPTOR_UI
2708	PUBCHEM_CID
7143	IUPHAR_LIGAND_ID
603	INN_ID
18D0SL7309	UNII
4405	MMSL
71849	MMSL
d00188	MMSL
002632	NDDF
387249003	SNOMEDCT_US
46009007	SNOMEDCT_US
4018769	VANDF

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
LEUKERAN	HUMAN PRESCRIPTION DRUG LABEL	1	69784-610	TABLET, FILM COATED	2 mg	ORAL	NDA	25 sections
LEUKERAN	HUMAN PRESCRIPTION DRUG LABEL	1	69784-610	TABLET, FILM COATED	2 mg	ORAL	NDA	25 sections
LEUKERAN	HUMAN PRESCRIPTION DRUG LABEL	1	76388-635	TABLET, FILM COATED	2 mg	ORAL	NDA	25 sections
LEUKERAN	HUMAN PRESCRIPTION DRUG LABEL	1	76388-635	TABLET, FILM COATED	2 mg	ORAL	NDA	25 sections
LEUKERAN	HUMAN PRESCRIPTION DRUG LABEL	1	80725-610	TABLET, FILM COATED	2 mg	ORAL	NDA	25 sections