dactinomycin 🐶 Veterinary Use | 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: 8.10
  • 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 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
fu (Fraction unbound in plasma) 0.65 % Kawashima H, Watanabe R, Esaki T, Kuroda M, Nagao C, Natsume-Kitatani Y, Ohashi R, Komura H, Mizuguchi K

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 536.58 42.40 89 3780 1221 63483932
Maternal exposure before pregnancy 348.97 42.40 83 3786 7520 63477633
Product use in unapproved indication 202.35 42.40 129 3740 178951 63306202
Febrile neutropenia 187.30 42.40 106 3763 118343 63366810
Off label use 175.73 42.40 209 3660 674253 62810900
Neutropenia 175.39 42.40 117 3752 174888 63310265
Drug resistance 175.01 42.40 62 3807 22871 63462282
Ototoxicity 141.02 42.40 29 3840 1333 63483820
Acute myeloid leukaemia 107.04 42.40 40 3829 17107 63468046
Disease recurrence 104.16 42.40 45 3824 27985 63457168
Ascites 102.92 42.40 50 3819 40678 63444475
Metastases to peritoneum 99.61 42.40 26 3843 3416 63481737
Second primary malignancy 94.36 42.40 30 3839 7923 63477230
Bone marrow failure 86.36 42.40 40 3829 29250 63455903
Malignant neoplasm progression 84.58 42.40 56 3813 82065 63403088
Mucosal inflammation 82.11 42.40 45 3824 46883 63438270
Metastases to lymph nodes 81.45 42.40 27 3842 8131 63477022
Venoocclusive liver disease 77.58 42.40 23 3846 4812 63480341
Metastases to liver 75.06 42.40 34 3835 23605 63461548
Venoocclusive disease 71.56 42.40 18 3851 2040 63483113
Thrombocytopenia 69.66 42.40 64 3805 151093 63334060
Disease progression 68.60 42.40 58 3811 122700 63362453
Neutropenic sepsis 66.35 42.40 28 3841 16410 63468743
Myelosuppression 65.61 42.40 31 3838 23672 63461481
Haematotoxicity 58.95 42.40 22 3847 9354 63475799
Tumour necrosis 43.06 42.40 10 3859 809 63484344

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
Second primary malignancy 149.39 37.60 44 2414 7842 34946631
Venoocclusive liver disease 135.91 37.60 41 2417 7925 34946548
Febrile neutropenia 113.19 37.60 86 2372 136763 34817710
Acute myeloid leukaemia 113.14 37.60 44 2414 18226 34936247
Bone marrow failure 87.08 37.60 42 2416 29211 34925262
Stomatitis 77.66 37.60 44 2414 42470 34912003
Delayed puberty 74.18 37.60 13 2445 214 34954259
Body height below normal 66.75 37.60 12 2446 230 34954243
Venoocclusive disease 63.12 37.60 18 2440 2849 34951624
Chromosome analysis abnormal 57.38 37.60 10 2448 159 34954314
Rhabdomyosarcoma recurrent 54.48 37.60 9 2449 102 34954371
Salivary gland cancer 51.01 37.60 10 2448 310 34954163
Off label use 48.91 37.60 97 2361 419427 34535046
Focal nodular hyperplasia 44.41 37.60 8 2450 155 34954318
Renal tubular disorder 42.78 37.60 15 2443 4628 34949845
Neutropenia 41.61 37.60 53 2405 156725 34797748
Basal cell naevus syndrome 40.15 37.60 6 2452 33 34954440
Drug resistance 39.78 37.60 24 2434 25903 34928570
Myelodysplastic syndrome 38.05 37.60 21 2437 19187 34935286

FDA Adverse Event Reporting System (Geriatric)

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
Febrile neutropenia 290.82 33.26 189 5513 230810 79507876
Venoocclusive liver disease 245.16 33.26 71 5631 11700 79726986
Second primary malignancy 189.54 33.26 61 5641 14289 79724397
Acute myeloid leukaemia 178.03 33.26 71 5631 30814 79707872
Venoocclusive disease 167.29 33.26 43 5659 4530 79734156
Neutropenia 154.21 33.26 142 5560 287568 79451118
Off label use 141.60 33.26 240 5462 906975 78831711
Drug resistance 134.81 33.26 64 5638 42149 79696537
Bone marrow failure 131.90 33.26 67 5635 51040 79687646
Product use in unapproved indication 119.52 33.26 116 5586 250243 79488443
Ascites 109.96 33.26 68 5634 75494 79663192
Stomatitis 101.69 33.26 84 5618 146673 79592013
Metastases to lymph nodes 100.66 33.26 35 5667 10362 79728324
Metastases to peritoneum 98.24 33.26 28 5674 4344 79734342
Malignant neoplasm progression 90.38 33.26 76 5626 135914 79602772
Mucosal inflammation 90.10 33.26 60 5642 75520 79663166
Salivary gland cancer 76.89 33.26 15 5687 445 79738241
Thrombocytopenia 71.13 33.26 91 5611 265168 79473518
Metastases to liver 64.03 33.26 34 5668 28280 79710406
Neoplasm progression 63.91 33.26 42 5660 51640 79687046
Myelosuppression 63.01 33.26 38 5664 40258 79698428
Rhabdomyosarcoma recurrent 59.75 33.26 10 5692 121 79738565
Renal tubular disorder 59.57 33.26 21 5681 6465 79732221
Disseminated intravascular coagulation 56.55 33.26 34 5668 35808 79702878
Febrile bone marrow aplasia 54.97 33.26 24 5678 12996 79725690
Haematotoxicity 54.03 33.26 25 5677 15494 79723192
Disease progression 53.74 33.26 66 5636 184296 79554390
Delayed puberty 49.39 33.26 9 5693 183 79738503
Chromosome analysis abnormal 46.91 33.26 9 5693 244 79738442
Acute lymphocytic leukaemia 41.52 33.26 15 5687 4954 79733732
Metastases to central nervous system 40.83 33.26 21 5681 16354 79722332
Basal cell naevus syndrome 40.05 33.26 6 5696 33 79738653
Ototoxicity 39.47 33.26 13 5689 3261 79735425
Encephalopathy 39.30 33.26 35 5667 67362 79671324
Ovarian failure 38.10 33.26 9 5693 667 79738019
Human chorionic gonadotropin increased 37.81 33.26 10 5692 1174 79737512
Tumour necrosis 37.36 33.26 11 5691 1911 79736775
Metastases to lung 36.02 33.26 20 5682 18143 79720543

FDA Adverse Event Reporting System (Pediatric)

None

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 | Suggest Off label Use Form| |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




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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
Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase Enzyme Kd 4.05 CHEMBL
Growth factor receptor-bound protein 2 Cytosolic other IC50 5.30 CHEMBL

External reference:

IDSource
4017964 VUID
N0000146314 NUI
D00214 KEGG_DRUG
3100 RXNORM
4017964 VANDF
C0010934 UMLSCUI
CHEBI:27666 CHEBI
CHEMBL1554 ChEMBL_ID
D003609 MESH_DESCRIPTOR_UI
DB00970 DRUGBANK_ID
1155 INN_ID
1CC1JFE158 UNII
2019 PUBCHEM_CID
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
DACTINOMYCIN Human Prescription Drug Label 1 55150-431 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 0.50 mg INTRAVENOUS ANDA 24 sections
DACTINOMYCIN Human Prescription Drug Label 1 55150-928 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
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 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