dactinomycin 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

None

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 545.54 41.36 91 4559 1552 90622245
Maternal exposure before pregnancy 330.96 41.36 83 4567 11130 90612667
Febrile neutropenia 259.97 41.36 137 4513 158212 90465585
Off label use 231.61 41.36 281 4369 1101971 89521826
Neutropenia 212.72 41.36 136 4514 224768 90399029
Product use in unapproved indication 187.04 41.36 147 4503 336089 90287708
Drug resistance 186.85 41.36 67 4583 30382 90593415
Ototoxicity 164.15 41.36 34 4616 1930 90621867
Acute myeloid leukaemia 121.24 41.36 44 4606 20596 90603201
Disease progression 119.45 41.36 83 4567 156532 90467265
Myelosuppression 118.87 41.36 57 4593 53534 90570263
Venoocclusive liver disease 112.42 41.36 31 4619 5962 90617835
Disease recurrence 111.60 41.36 49 4601 37604 90586193
Ascites 106.54 41.36 51 4599 47689 90576108
Mucosal inflammation 103.20 41.36 53 4597 57572 90566225
Second primary malignancy 99.71 41.36 32 4618 10346 90613451
Metastases to peritoneum 94.39 41.36 25 4625 4130 90619667
Bone marrow failure 86.08 41.36 39 4611 32182 90591615
Malignant neoplasm progression 82.23 41.36 57 4593 106813 90516984
Metastases to liver 80.55 41.36 36 4614 28771 90595026
Metastases to lymph nodes 76.47 41.36 27 4623 11662 90612135
Thrombocytopenia 76.32 41.36 72 4578 208653 90415144
Neoplasm progression 74.12 41.36 39 4611 44447 90579350
Anisometropia 67.04 41.36 10 4640 78 90623719
Venoocclusive disease 66.54 41.36 17 4633 2438 90621359
Febrile bone marrow aplasia 65.63 41.36 23 4627 9715 90614082
Neutropenic sepsis 64.94 41.36 27 4623 18103 90605694
Haematotoxicity 59.97 41.36 23 4627 12512 90611285
Metastases to central nervous system 52.49 41.36 23 4627 17519 90606278
Eustachian tube dysfunction 50.95 41.36 11 4639 761 90623036
Anaemia 50.06 41.36 75 4575 352727 90271070
Deafness 50.02 41.36 24 4626 22490 90601307
Tumour necrosis 48.10 41.36 11 4639 990 90622807
Gastrointestinal toxicity 43.96 41.36 17 4633 9450 90614347
Metastasis 43.29 41.36 15 4635 6122 90617675

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 141.62 38.79 43 2629 9532 42609131
Venoocclusive liver disease 138.51 38.79 43 2629 10259 42608404
Acute myeloid leukaemia 120.09 38.79 47 2625 22209 42596454
Febrile neutropenia 119.53 38.79 96 2576 185607 42433056
Stomatitis 94.51 38.79 51 2621 50278 42568385
Bone marrow failure 86.71 38.79 42 2630 33051 42585612
Delayed puberty 75.44 38.79 13 2659 218 42618445
Venoocclusive disease 72.76 38.79 21 2651 3894 42614769
Neutropenia 69.01 38.79 73 2599 199358 42419305
Body height below normal 68.12 38.79 12 2660 230 42618433
Rhabdomyosarcoma recurrent 67.04 38.79 11 2661 135 42618528
Chromosome analysis abnormal 63.15 38.79 11 2661 197 42618466
Off label use 56.45 38.79 123 2549 638212 41980451
Salivary gland cancer 51.70 38.79 10 2662 325 42618338
Myelodysplastic syndrome 45.28 38.79 24 2648 22721 42595942
Focal nodular hyperplasia 44.90 38.79 8 2664 164 42618499
Renal tubular disorder 43.65 38.79 15 2657 4894 42613769
Mucosal inflammation 41.37 38.79 30 2642 49344 42569319
Basal cell naevus syndrome 40.40 38.79 6 2666 36 42618627
Osteopenia 40.04 38.79 15 2657 6263 42612400
Neoplasm progression 39.84 38.79 24 2648 28976 42589687

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 373.68 32.57 233 6396 316534 110266136
Venoocclusive liver disease 257.09 32.57 75 6554 15132 110567538
Neutropenia 223.23 32.57 182 6447 374438 110208232
Off label use 196.11 32.57 332 6297 1499853 109082817
Acute myeloid leukaemia 193.05 32.57 76 6553 38034 110544636
Second primary malignancy 190.30 32.57 62 6567 18006 110564664
Myelosuppression 140.70 32.57 81 6548 94259 110488411
Drug resistance 136.82 32.57 67 6562 56307 110526363
Bone marrow failure 132.21 32.57 66 6563 57782 110524888
Mucosal inflammation 131.37 32.57 78 6551 96063 110486607
Venoocclusive disease 123.72 32.57 35 6594 6315 110576355
Product use in unapproved indication 117.49 32.57 139 6490 447238 110135432
Neoplasm progression 108.55 32.57 60 6569 64535 110518135
Disease progression 97.86 32.57 95 6534 243939 110338731
Stomatitis 96.93 32.57 99 6530 270143 110312527
Thrombocytopenia 95.81 32.57 111 6518 348774 110233896
Metastases to peritoneum 91.80 32.57 27 6602 5583 110577087
Malignant neoplasm progression 85.48 32.57 76 6553 174491 110408179
Ascites 83.74 32.57 58 6571 92750 110489920
Metastases to lymph nodes 83.21 32.57 32 6597 15000 110567670
Febrile bone marrow aplasia 78.56 32.57 32 6597 17433 110565237
Salivary gland cancer 77.93 32.57 15 6614 497 110582173
Rhabdomyosarcoma recurrent 66.38 32.57 11 6618 151 110582519
Metastases to liver 65.32 32.57 35 6594 35351 110547319
Anisometropia 64.51 32.57 10 6619 87 110582583
Deafness 62.53 32.57 31 6598 26678 110555992
Renal tubular disorder 60.40 32.57 21 6608 7408 110575262
Ototoxicity 59.42 32.57 18 6611 4113 110578557
Metastases to central nervous system 54.95 32.57 27 6602 22790 110559880
Metastasis 54.48 32.57 20 6609 8247 110574423
Haematotoxicity 53.94 32.57 26 6603 21056 110561614
Chromosome analysis abnormal 53.75 32.57 10 6619 275 110582395
Eustachian tube dysfunction 50.22 32.57 11 6618 695 110581975
Delayed puberty 50.08 32.57 9 6620 203 110582467
Ovarian failure 46.67 32.57 11 6618 965 110581705
Anaemia 42.40 32.57 98 6531 546988 110035682
Gastrointestinal toxicity 41.97 32.57 18 6611 11130 110571540
Tumour necrosis 41.06 32.57 12 6617 2424 110580246
Neuropathy peripheral 40.86 32.57 52 6577 179225 110403445
Basal cell naevus syndrome 40.66 32.57 6 6623 36 110582634
Astigmatism 40.55 32.57 11 6618 1698 110580972
Encephalopathy 39.04 32.57 35 6594 81020 110501650
Cardiotoxicity 37.76 32.57 19 6610 16862 110565808
Disseminated intravascular coagulation 35.33 32.57 25 6604 41261 110541409
Myelodysplastic syndrome 35.13 32.57 24 6605 37460 110545210
Disease recurrence 34.85 32.57 29 6600 60755 110521915
Metastases to lung 34.85 32.57 20 6609 23043 110559627
Acute lymphocytic leukaemia 34.52 32.57 13 6616 5752 110576918
Fanconi syndrome 32.72 32.57 11 6618 3508 110579162

FDA Adverse Event Reporting System (Pediatric)

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
Pulmonary nocardiosis 31.85 15.48 4 3 8 113938

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 D000890 Anti-Infective Agents
MeSH PA D000900 Anti-Bacterial Agents
MeSH PA D000903 Antibiotics, Antineoplastic
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D011500 Protein Synthesis Inhibitors
MeSH PA D019384 Nucleic Acid Synthesis Inhibitors
FDA EPC N0000180850 Actinomycin
CHEBI has role CHEBI:25435 mutagen
CHEBI has role CHEBI:35610 antineoplastic agent

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
C0010934 UMLSCUI
CHEBI:27666 CHEBI
CHEMBL1554 ChEMBL_ID
D003609 MESH_DESCRIPTOR_UI
DB00970 DRUGBANK_ID
1155 INN_ID
1CC1JFE158 UNII
457193 PUBCHEM_CID
174221 MMSL
4530 MMSL
d00203 MMSL
002657 NDDF
387353003 SNOMEDCT_US
64127001 SNOMEDCT_US
4017964 VANDF

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
dactinomycin HUMAN PRESCRIPTION DRUG LABEL 1 39822-2100 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 0.50 mg INTRAVENOUS ANDA 25 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
Dactinomycin HUMAN PRESCRIPTION DRUG LABEL 1 71288-129 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 0.50 mg INTRAVENOUS ANDA 24 sections