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

Stem definition	Drug id	CAS RN
antibiotics, produced by Streptomyces strains	774	50-76-0

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: Actinomycin D dactinomycin Actactinomycin A IV Actinomycin 7 Chounghwamycin B Dactinomycin D Dilactone actinomycin D acid Dilactone actinomycindioic D acid meractinomycin Oncostatin K	A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015) Molecular weight: 1255.44 Formula: C62H86N12O16 CLOGP: 8.05 LIPINSKI: 3 HAC: 28 HDO: 5 TPSA: 355.54 ALOGS: -4.80 ROTB: 8

Molecule

Description

Molfile Inchi Smiles

Synonyms:

Actinomycin D
dactinomycin
Actactinomycin A IV
Actinomycin 7
Chounghwamycin B
Dactinomycin D
Dilactone actinomycin D acid
Dilactone actinomycindioic D acid
meractinomycin
Oncostatin K

A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015)

Molecular weight: 1255.44
Formula: C62H86N12O16
CLOGP: 8.05
LIPINSKI: 3
HAC: 28
HDO: 5
TPSA: 355.54
ALOGS: -4.80
ROTB: 8

Drug dosage:

None

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	3	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	0.50 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	10 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.01 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD

Approvals:

Date	Agency	Company	Orphan
Dec. 10, 1964	FDA	RECORDATI RARE

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
Ovarian failure	541.49	39.28	89	3035	1043	46681895
Maternal exposure before pregnancy	385.14	39.28	83	3041	4398	46678540
Product use in unapproved indication	190.98	39.28	101	3023	90172	46592766
Off label use	158.99	39.28	158	2966	379683	46303255
Drug resistance	143.42	39.28	51	3073	17317	46665621
Febrile neutropenia	143.08	39.28	85	3039	94542	46588396
Nephroblastoma	127.75	39.28	19	3105	107	46682831
Choriocarcinoma	121.54	39.28	18	3106	98	46682840
Neutropenia	108.83	39.28	84	3040	143120	46539818
Disease recurrence	104.06	39.28	41	3083	18430	46664508
Ototoxicity	98.47	39.28	21	3103	1048	46681890
Acute myeloid leukaemia	92.30	39.28	36	3088	15742	46667196
Bone marrow failure	82.34	39.28	40	3084	29629	46653309
Second primary malignancy	76.50	39.28	25	3099	6559	46676379
Venoocclusive disease	75.77	39.28	19	3105	1937	46681001
Neutropenic sepsis	75.19	39.28	29	3095	12295	46670643
Malignant neoplasm progression	62.47	39.28	44	3080	64882	46618056
Gestational trophoblastic tumour	62.27	39.28	9	3115	40	46682898
Mucosal inflammation	56.07	39.28	34	3090	38942	46643996
Febrile bone marrow aplasia	56.00	39.28	20	3104	6842	46676096
Venoocclusive liver disease	48.80	39.28	16	3108	4235	46678703
Haematotoxicity	48.37	39.28	18	3106	6915	46676023
Ascites	47.75	39.28	30	3094	36554	46646384
Metastases to peritoneum	47.38	39.28	14	3110	2634	46680304
Desmoplastic small round cell tumour	44.95	39.28	8	3116	152	46682786
Tumour necrosis	42.69	39.28	10	3114	765	46682173
Metastases to liver	41.43	39.28	22	3102	19563	46663375
Metastases to lung	40.81	39.28	18	3106	10678	46672260

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
Venoocclusive liver disease	132.43	39.17	38	1944	6575	29943921
Second primary malignancy	129.41	39.17	37	1945	6319	29944177
Febrile neutropenia	117.73	39.17	78	1904	106615	29843881
Acute myeloid leukaemia	105.67	39.17	41	1941	17965	29932531
Bone marrow failure	91.96	39.17	43	1939	29742	29920754
Delayed puberty	78.07	39.17	13	1969	166	29950330
Body height below normal	73.32	39.17	13	1969	245	29950251
Off label use	68.74	39.17	83	1899	249207	29701289
Venoocclusive disease	61.39	39.17	17	1965	2573	29947923
Renal tubular disorder	50.35	39.17	17	1965	4989	29945507
Rhabdomyosarcoma recurrent	48.72	39.17	8	1974	93	29950403
Focal nodular hyperplasia	45.10	39.17	8	1974	151	29950345
Basal cell naevus syndrome	41	39.17	6	1976	30	29950466

Pharmacologic Action:

Source	Code	Description
ATC	L01DA01	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS CYTOTOXIC ANTIBIOTICS AND RELATED SUBSTANCES Actinomycines
FDA MoA	N0000000150	Protein Synthesis Inhibitors
FDA MoA	N0000000233	Nucleic Acid Synthesis Inhibitors
MeSH PA	D000900	Anti-Bacterial Agents
MeSH PA	D000890	Anti-Infective Agents
MeSH PA	D000903	Antibiotics, Antineoplastic
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D019384	Nucleic Acid Synthesis Inhibitors
MeSH PA	D011500	Protein Synthesis Inhibitors
FDA EPC	N0000180850	Actinomycin
CHEBI has role	CHEBI:25435	mutagens

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Ewing's sarcoma	indication	76909002	DOID:3369
Rhabdomyosarcoma	indication	302847003	DOID:3247
Nephroblastoma	indication	302849000	DOID:2154
Malignant tumor of testis	indication	363449006	DOID:2998
Gestational trophoblastic neoplasia	indication	609519004	DOID:3590
Kaposi's sarcoma	off-label use	109385007
Ovarian Germ Cell Tumor Carcinoma	off-label use
Herpes zoster	contraindication	4740000	DOID:8536
Hepatic vein thrombosis	contraindication	38739001	DOID:11512
Acute infectious disease	contraindication	63171007
Leukopenia	contraindication	84828003	DOID:615
Liver function tests abnormal	contraindication	166603001
Disease of liver	contraindication	235856003	DOID:409
Anemia	contraindication	271737000	DOID:2355
Pregnancy, function	contraindication	289908002
Thrombocytopenic disorder	contraindication	302215000	DOID:1588
Neutropenic disorder	contraindication	303011007	DOID:1227
Aplastic anemia	contraindication	306058006	DOID:12449
Bone marrow depression	contraindication	307762000
Varicella-zoster virus infection	contraindication	309465005
Ascites	contraindication	389026000
Breastfeeding (mother)	contraindication	413712001
Exposure to varicella	contraindication	444453009

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	4.31	Basic

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])	Bioact source	MoA source
Growth factor receptor-bound protein 2	Cytosolic other	P62993	GRB2_HUMAN		IC50	5.30	CHEMBL
Discoidin domain-containing receptor 2	Kinase	Q16832	DDR2_HUMAN		IC50	5.05	CHEMBL
DNA	DNA			OTHER			DRUG LABEL	DRUG LABEL
Growth factor receptor-bound protein 2	Cytosolic other		GRB2_MOUSE		IC50	5.30	CHEMBL

External reference:

ID	Source
4017964	VUID
N0000146314	NUI
D00214	KEGG_DRUG
4017964	VANDF
C0010934	UMLSCUI
CHEBI:27666	CHEBI
CHEMBL1554	ChEMBL_ID
457193	PUBCHEM_CID
DB00970	DRUGBANK_ID
D003609	MESH_DESCRIPTOR_UI
1155	INN_ID
1CC1JFE158	UNII
3100	RXNORM
174221	MMSL
4530	MMSL
d00203	MMSL
002657	NDDF
387353003	SNOMEDCT_US
64127001	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
dactinomycin	HUMAN PRESCRIPTION DRUG LABEL	1	39822-2100	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	0.50 mg	INTRAVENOUS	ANDA	20 sections
Dactinomycin	HUMAN PRESCRIPTION DRUG LABEL	1	42658-008	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	0.50 mg	INTRAVENOUS	ANDA	24 sections
Cosmegen	HUMAN PRESCRIPTION DRUG LABEL	1	55292-811	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	0.50 mg	INTRAVENOUS	NDA	24 sections
Dactinomycin	HUMAN PRESCRIPTION DRUG LABEL	1	66993-489	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	0.50 mg	INTRAVENOUS	NDA authorized generic	16 sections
Dactinomycin	HUMAN PRESCRIPTION DRUG LABEL	1	67457-513	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	0.50 mg	INTRAVENOUS	ANDA	25 sections
Dactinomycin	HUMAN PRESCRIPTION DRUG LABEL	1	67457-928	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	0.50 mg	INTRAVENOUS	ANDA	25 sections
Dactinomycin	HUMAN PRESCRIPTION DRUG LABEL	1	71288-129	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	0.50 mg	INTRAVENOUS	ANDA	24 sections