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	217.42	36.65	65	2506	15646	46667845
Malignant transformation	142.49	36.65	23	2548	292	46683199
Brain oedema	127.64	36.65	41	2530	12437	46671054
Febrile neutropenia	104.95	36.65	65	2506	94562	46588929
Mucosal inflammation	100.60	36.65	47	2524	38929	46644562
Acute myeloid leukaemia	99.18	36.65	36	2535	15742	46667749
Stem cell transplant	81.39	36.65	19	2552	1747	46681744
Second primary malignancy	77.09	36.65	24	2547	6560	46676931
Pneumocephalus	60.88	36.65	10	2561	142	46683349
Thrombocytopenia	57.85	36.65	51	2520	126530	46556961
Enterococcal infection	51.66	36.65	18	2553	6969	46676522
Intracranial hypotension	46.91	36.65	9	2562	320	46683171
Progressive multifocal leukoencephalopathy	46.57	36.65	19	2552	11327	46672164
Venoocclusive disease	44.69	36.65	12	2559	1944	46681547
Cardiomyopathy acute	44.04	36.65	8	2563	210	46683281
Pneumocystis jirovecii pneumonia	41.17	36.65	19	2552	15229	46668262
Chronic myelomonocytic leukaemia	40.88	36.65	8	2563	316	46683175
JC virus infection	37.05	36.65	10	2561	1652	46681839

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	329.19	32.26	120	4582	18658	29929118
Venoocclusive liver disease	243.34	32.26	74	4628	6539	29941237
Malignant transformation	225.17	32.26	45	4657	668	29947108
Acute myeloid leukaemia	167.70	32.26	73	4629	17933	29929843
Febrile neutropenia	146.29	32.26	126	4576	106567	29841209
Brain oedema	127.68	32.26	54	4648	12344	29935432
Off label use	126.72	32.26	174	4528	249116	29698660
Second primary malignancy	123.80	32.26	44	4658	6312	29941464
Pneumocephalus	118.57	32.26	19	4683	68	29947708
Blood stem cell transplant failure	88.49	32.26	19	4683	406	29947370
Basal cell carcinoma	78.81	32.26	42	4660	16026	29931750
Mucosal inflammation	72.31	32.26	50	4652	30444	29917332
Venoocclusive disease	62.29	32.26	21	4681	2569	29945207
Malignant neoplasm progression	61.87	32.26	66	4636	72221	29875555
Aspergillus infection	59.56	32.26	30	4672	10184	29937592
Myositis	59.11	32.26	30	4672	10347	29937429
Hepatic infection fungal	55.60	32.26	11	4691	154	29947622
Transformation to acute myeloid leukaemia	55.11	32.26	14	4688	632	29947144
Bronchopulmonary aspergillosis	54.35	32.26	30	4672	12254	29935522
Product use in unapproved indication	53.93	32.26	62	4640	73631	29874145
Diffuse large B-cell lymphoma	51.57	32.26	25	4677	7816	29939960
Stem cell transplant	50.14	32.26	17	4685	2114	29945662
Metastases to muscle	47.05	32.26	10	4692	203	29947573
Metastases to retroperitoneum	46.82	32.26	10	4692	208	29947568
Febrile bone marrow aplasia	44.92	32.26	23	4679	8074	29939702
Human herpesvirus 8 infection	44.63	32.26	12	4690	677	29947099
Neutropenic sepsis	42.75	32.26	25	4677	11384	29936392
Metastases to spleen	42.31	32.26	10	4692	333	29947443
Expanded disability status scale score increased	41.97	32.26	9	4693	191	29947585
Cytomegalovirus infection	40.70	32.26	32	4670	23642	29924134
Metastases to bone marrow	38.39	32.26	10	4692	499	29947277
Enteritis	37.22	32.26	19	4683	6626	29941150
B-cell lymphoma recurrent	36.07	32.26	10	4692	633	29947143
Intentional product use issue	34.21	32.26	35	4667	36405	29911371
Staphylococcal infection	33.90	32.26	32	4670	30192	29917584
Intracranial hypotension	33.86	32.26	8	4694	266	29947510
Retinal haemorrhage	33.85	32.26	16	4686	4727	29943049
Pneumocystis jirovecii pneumonia	33.50	32.26	25	4677	17095	29930681
Cytopenia	33.35	32.26	19	4683	8237	29939539

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
DNA	DNA			OTHER				DRUG LABEL	DRUG LABEL

External reference:

ID	Source
4020993	VUID
N0000148463	NUI
D00254	KEGG_DRUG
4018136	VANDF
4020993	VANDF
C1516301	UMLSCUI
CHEBI:3423	CHEBI
CHEMBL513	ChEMBL_ID
DB00262	DRUGBANK_ID
D002330	MESH_DESCRIPTOR_UI
2959	INN_ID
2578	PUBCHEM_CID
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

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