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

Stem definitionDrug idCAS RN
antibiotics, produced by Streptomyces strains 774 50-76-0

Description:

MoleculeDescription

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:

PropertyValueReference
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 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD

Approvals:

DateAgencyCompanyOrphan
Dec. 10, 1964 FDA RECORDATI RARE

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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 termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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:

SourceCodeDescription
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)

DiseaseRelationSNOMED_IDDOID
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 levelDissociation constantType (acidic/basic)
pKa1 4.31 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Growth factor receptor-bound protein 2 Cytosolic other IC50 5.30 CHEMBL
Discoidin domain-containing receptor 2 Kinase IC50 5.05 CHEMBL
DNA DNA OTHER DRUG LABEL DRUG LABEL
Growth factor receptor-bound protein 2 Cytosolic other IC50 5.30 CHEMBL

External reference:

IDSource
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:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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