carmustine Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
antineoplastic, alkylating agents, (beta-chloroethyl)amine derivatives	512	154-93-8

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: carmustine becenun carmubris carmustin nitrumon	A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed) Molecular weight: 214.05 Formula: C5H9Cl2N3O2 CLOGP: 1.32 LIPINSKI: 0 HAC: 5 HDO: 1 TPSA: 61.77 ALOGS: -2.15 ROTB: 5 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

carmustine
becenun
carmubris
carmustin
nitrumon

A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)

Molecular weight: 214.05
Formula: C5H9Cl2N3O2
CLOGP: 1.32
LIPINSKI: 0
HAC: 5
HDO: 1
TPSA: 61.77
ALOGS: -2.15
ROTB: 5

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)	3.80 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	0.50 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.55 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	11.50 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	1.20 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	78 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.23 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	0.37 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
March 7, 1977	FDA	EMCURE PHARMS LTD

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
Myelodysplastic syndrome	236.25	40.08	69	2646	16591	53329760
Malignant transformation	141.48	40.08	23	2692	333	53346018
Brain oedema	127.46	40.08	41	2674	13517	53332834
Febrile neutropenia	113.65	40.08	69	2646	104867	53241484
Mucosal inflammation	109.30	40.08	50	2665	42734	53303617
Acute myeloid leukaemia	103.22	40.08	37	2678	16895	53329456
Stem cell transplant	82.05	40.08	19	2696	1826	53344525
Second primary malignancy	77.06	40.08	24	2691	7108	53339243
Pneumocephalus	61.35	40.08	10	2705	147	53346204
Thrombocytopenia	61.29	40.08	53	2662	138674	53207677
Enterococcal infection	55.45	40.08	19	2696	7579	53338772
Haematotoxicity	54.73	40.08	19	2696	7878	53338473
Venoocclusive disease	54.70	40.08	14	2701	2041	53344310
Progressive multifocal leukoencephalopathy	50.25	40.08	20	2695	12109	53334242
Intracranial hypotension	47.95	40.08	9	2706	308	53346043
Chronic myelomonocytic leukaemia	47.29	40.08	9	2706	332	53346019
Aplasia	44.82	40.08	14	2701	4178	53342173
Cardiomyopathy acute	44.31	40.08	8	2707	220	53346131
Bacteraemia	42.24	40.08	19	2696	15530	53330821
Pneumocystis jirovecii pneumonia	41.30	40.08	19	2696	16359	53329992

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
Myelodysplastic syndrome	335.55	31.25	124	5007	19914	32488481
Venoocclusive liver disease	243.42	31.25	76	5055	7289	32501106
Malignant transformation	224.35	31.25	46	5085	777	32507618
Acute myeloid leukaemia	198.85	31.25	84	5047	19090	32489305
Febrile neutropenia	164.96	31.25	142	4989	119424	32388971
Second primary malignancy	127.22	31.25	46	5085	6895	32501500
Brain oedema	125.08	31.25	54	5077	12906	32495489
Off label use	119.00	31.25	189	4942	306131	32202264
Pneumocephalus	114.19	31.25	19	5112	90	32508305
Blood stem cell transplant failure	88.43	31.25	19	5112	405	32507990
Mucosal inflammation	77.10	31.25	54	5077	33380	32475015
Basal cell carcinoma	75.08	31.25	42	5089	17526	32490869
Venoocclusive disease	72.83	31.25	24	5107	2722	32505673
Aspergillus infection	70.29	31.25	35	5096	11539	32496856
Malignant neoplasm progression	60.48	31.25	68	5063	78428	32429967
Myositis	59.56	31.25	31	5100	11204	32497191
Febrile bone marrow aplasia	58.76	31.25	28	5103	8387	32500008
Bronchopulmonary aspergillosis	53.82	31.25	31	5100	13656	32494739
Transformation to acute myeloid leukaemia	53.80	31.25	14	5117	692	32507703
Hepatic infection fungal	53.77	31.25	11	5120	183	32508212
Stem cell transplant	53.23	31.25	18	5113	2209	32506186
Product use in unapproved indication	51.50	31.25	66	5065	87138	32421257
Neutropenic sepsis	50.57	31.25	29	5102	12670	32495725
Diffuse large B-cell lymphoma	49.63	31.25	25	5106	8437	32499958
Metastases to muscle	46.63	31.25	10	5121	211	32508184
Metastases to retroperitoneum	46.06	31.25	10	5121	224	32508171
Enteritis	44.20	31.25	22	5109	7239	32501156
Human herpesvirus 8 infection	42.17	31.25	12	5119	831	32507564
Metastases to spleen	41.45	31.25	10	5121	362	32508033
Cytomegalovirus infection	40.59	31.25	33	5098	25431	32482964
B-cell lymphoma recurrent	40.21	31.25	11	5120	659	32507736
Cytopenia	40.11	31.25	23	5108	10041	32498354
Expanded disability status scale score increased	39.95	31.25	9	5122	240	32508155
Metastases to bone marrow	38.10	31.25	10	5121	511	32507884
Intentional product use issue	34.93	31.25	38	5093	42173	32466222
Intracranial hypotension	33.78	31.25	8	5123	267	32508128
Staphylococcal infection	33.69	31.25	33	5098	32406	32475989
Retinal haemorrhage	32.90	31.25	16	5115	5005	32503390
Myelosuppression	31.98	31.25	21	5110	11655	32496740

Pharmacologic Action:

Source	Code	Description
ATC	L01AD01	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS ALKYLATING AGENTS Nitrosoureas
FDA MoA	N0000000236	Alkylating Activity
FDA EPC	N0000175558	Alkylating Drug
CHEBI has role	CHEBI:35610	cytostatic
MeSH PA	D000477	Alkylating Agents
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D018906	Antineoplastic Agents, Alkylating
MeSH PA	D009676	Noxae

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Glioma, malignant	indication	74532006
Diffuse non-Hodgkin's lymphoma, large cell	indication	109969005
Multiple myeloma	indication	109989006	DOID:9538
Hodgkin's disease	indication	118599009
Non-Hodgkin's lymphoma	indication	118601006
Glioblastoma multiforme of brain	indication	276828006	DOID:3073
Malignant neoplasm of brain	indication	428061005	DOID:1319
Astrocytoma, anaplastic	off-label use	55353007	DOID:3078
Allogeneic bone marrow transplantation	off-label use	58390007
Mycosis fungoides	off-label use	118618005
Cerebral edema	contraindication	2032001
Mycosis	contraindication	3218000	DOID:1564
Meningitis	contraindication	7180009	DOID:9471
Disorder of lung	contraindication	19829001	DOID:850
Retinal hemorrhage	contraindication	28998008
Viral disease	contraindication	34014006	DOID:934
Infectious disease	contraindication	40733004
Fibrosis of lung	contraindication	51615001	DOID:3770
Epilepsy	contraindication	84757009	DOID:1826
Leukopenia	contraindication	84828003	DOID:615
Bacterial infectious disease	contraindication	87628006
Kidney disease	contraindication	90708001	DOID:557
Acute leukemia, disease	contraindication	91855006	DOID:12603
Liver function tests abnormal	contraindication	166603001
Obstructive hydrocephalus	contraindication	230746009	DOID:14159
Disease of liver	contraindication	235856003	DOID:409
Anemia	contraindication	271737000	DOID:2355
Pregnancy, function	contraindication	289908002
Thrombocytopenic disorder	contraindication	302215000	DOID:1588
Bone marrow depression	contraindication	307762000
Breastfeeding (mother)	contraindication	413712001
Abscess of brain	contraindication	441806004
Protozoal Infection	contraindication
Significant Bleeding	contraindication
Pulmonary Infiltrates	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	11.09	acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Glutathione reductase, mitochondrial	Enzyme	P00390	GSHR_HUMAN	INHIBITOR	IC50	5.09		CHEMBL	CHEMBL

External reference:

ID	Source
4020993	VUID
N0000148463	NUI
D00254	KEGG_DRUG
C0007257	UMLSCUI
CHEBI:3423	CHEBI
CHEMBL513	ChEMBL_ID
DB00262	DRUGBANK_ID
D002330	MESH_DESCRIPTOR_UI
2578	PUBCHEM_CID
2959	INN_ID
6800	IUPHAR_LIGAND_ID
U68WG3173Y	UNII
2105	RXNORM
251354	MMSL
4360	MMSL
d01342	MMSL
002640	NDDF
387281007	SNOMEDCT_US
51326002	SNOMEDCT_US
786790001	SNOMEDCT_US
4018136	VANDF
4020993	VANDF

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Gliadel	HUMAN PRESCRIPTION DRUG LABEL	1	24338-050	WAFER	7.70 mg	INTRACAVITARY	NDA	25 sections