ACT;ACT D;Actactinomycin a Iv;Actinomycin 11 Cosmegen;Actinomycin 7;Actinomycin Aiv;Actinomycin C1;ACTINOMYCIN D;Actinomycin I;Actinomycin I1;Actinomycin Iv;Actinomycin X 1;Actinomycindioic D Acid, Dilactone;ACTO-D;Chounghwamycin B;Cosmegen;Dactinomycin D;Dilactone Actinomycin D Acid;Dilactone Actinomycindioic D Acid;HBF 386 Meractinomycin;Lyovac Cosmegen;Meractinomycin;Oncostatin K;Oxamide;

AD;Antibiotic From Streptomyces Parvullus;Dactinomicina [INN-Spanish];Dactinomycine [INN-French];Dactinomycinum [INN-Latin];

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)

• Bedford laboratories div ben venue laboratories inc
• Lundbeck inc

Synthesis Reference

Not Available

General Reference

Sobell HM: Actinomycin and DNA transcription. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5328-31. Pubmed Turan T, Karacay O, Tulunay G, Boran N, Koc S, Bozok S, Kose MF: Results with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) chemotherapy in gestational trophoblastic neoplasia. Int J Gynecol Cancer. 2006 May-Jun;16(3):1432-8. Pubmed Abd El-Aal HH, Habib EE, Mishrif MM: Wilms’ tumor: the experience of the pediatric unit of Kasr El-Aini center of radiation oncology and nuclear medicine (NEMROCK). J Egypt Natl Canc Inst. 2005 Dec;17(4):308-14. Pubmed Khatua S, Nair CN, Ghosh K: Immune-mediated thrombocytopenia following dactinomycin therapy in a child with alveolar rhabdomyosarcoma: the unresolved issues. J Pediatr Hematol Oncol. 2004 Nov;26(11):777-9. Pubmed

Form	Route	Strength
Powder, for solution	Intravenous

Unit description	Cost	Unit
Cosmegen 0.5 mg vial	684.36 USD	vial

Type	small molecule

Classes

Lactams Benzoyl Derivatives Benzamides

Substructures

Carboxylic Acids and Derivatives Acetates Lactones Amino Ketones Aliphatic and Aryl Amines Pyrrolidines Ethers Benzene and Derivatives Heterocyclic compounds Aromatic compounds Carboxamides and Derivatives Lactams Imines Benzoyl Derivatives Benzamides

Cancer 癌症;

Indication	For the treatment of Wilms' tumor, childhood rhabdomyosarcoma, Ewing's sarcoma and metastatic, nonseminomatous testicular cancer as part of a combination chemotherapy and/or multi-modality treatment regimen
Pharmacodynamics	Generally, the actinomycins exert an inhibitory effect on gram-positive and gram-negative bacteria and on some fungi. However, the toxic properties of the actinomycins (including dactinomycin) in relation to antibacterial activity are such as to preclude their use as antibiotics in the treatment of infectious diseases. Because the actinomycins are cytotoxic, they have an antineoplastic effect which has been demonstrated in experimental animals with various types of tumor implant. This cytotoxic action is the basis for their use in the treatment of certain types of cancer. Dactinomycin is believed to produce its cytotoxic effects by binding DNA and inhibiting RNA synthesis.
Mechanism of action	Good evidence exists that this drug bind strongly, but reversibly, to DNA, interfering with synthesis of RNA (prevention of RNA polymerase elongation) and, consequently, with protein synthesis.
Absorption	poorly absorbed from gastrointestinal tract
Volume of distribution	Not Available
Protein binding	5%
Metabolism	hepatic
Route of elimination	Not Available
Half life	36 hours
Clearance	Not Available
Toxicity	hepatoxicity
Affected organisms	Humans and other mammals
Pathways	Not Available

Properties
State	solid
Melting point	241.5 - 243 oC
Experimental Properties	Property Value Source water solubility Soluble at 10°C PhysProp logP 1.6 PhysProp
Predicted Properties	Property Value Source water solubility 2.00e-02 g/l ALOGPS logP 2.76 ALOGPS logP -0.10 ChemAxon Molconvert logS -4.80 ALOGPS pKa 11.10 ChemAxon Molconvert hydrogen acceptor count 16 ChemAxon Molconvert hydrogen donor count 5 ChemAxon Molconvert polar surface area 355.54 ChemAxon Molconvert rotatable bond count 8 ChemAxon Molconvert refractivity 326.17 ChemAxon Molconvert polarizability 131.82 ChemAxon Molconvert

Drug	Interaction
Trastuzumab	Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.

Not Available