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Dactinomycin

July 24, 2017
Common Name

Dactinomycin Description

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

MOLSDFPDBSMILESInChI

Synonyms

Value Source 2-amino-N,N'-bis(hexadecahydro-2,5,9-trimethyl-6,13-bis(1-methylethyl)-1,4,7,11,14-pentaoxo-1H-pyrrolo(2,1-i)(1,4,7,10,13)oxatetra-azacyclohexadecin-10-yl)-4,6-dimethyl-3-oxo-3H-phenoxazine-1,9-dicarboxamideChEBI ActDChEBI Actinomycin C1ChEBI Actinomycin IVChEBI Actinomycin DHMDB Ac-deMeSH CosmegenMeSH Lyovac, cosmegenMeSH MSD Brand OF dactinomycinMeSH Lemery brand OF dactinomycinMeSH Lyovac-cosmegenMeSH Merck brand OF dactinomycinMeSH Merck sharp and dohme brand OF dactinomycinMeSH Cosmegen lyovacMeSH MeractinomycinMeSH ActinomycinMeSH Merck frosst brand OF dactinomycinMeSH

Chemical Formlia

C62H86N12O16 Average Molecliar Weight

1255.417 Monoisotopic Molecliar Weight

1254.628474764 IUPAC Name

N1,N9-bis[(6S,9R,10S,13R,18aS)-2,5,9-trimethyl-1,4,7,11,14-pentaoxo-6,13-bis(propan-2-yl)-hexadecahydro-1H-pyrrolo[2,1-i]1-oxa-4,7,10,13-tetraazacyclohexadecan-10-yl]-2-amino-4,6-dimethyl-3-oxo-3H-phenoxazine-1,9-dicarboxamide Traditional Name

actinomycin D CAS Registry Number

50-76-0 SMILES

[H][C@@]12CCCN1C(=O)[C@H](NC(=O)[C@@H](NC(=O)C1=C3N=C4C(OC3=C(C)C=C1)=C(C)C(=O)C(N)=C4C(=O)N[C@H]1[C@@H](C)OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@]3([H])CCCN3C(=O)[C@H](NC1=O)C(C)C)[C@@H](C)OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C2=O)C(C)C

InChI Identifier

InChI=1S/C62H86N12O16/c1-27(2)42-59(84)73-23-17-19-36(73)57(82)69(13)25-38(75)71(15)48(29(5)6)61(86)88-33(11)44(55(80)65-42)67-53(78)35-22-21-31(9)51-46(35)64-47-40(41(63)50(77)32(10)52(47)90-51)54(79)68-45-34(12)89-62(87)49(30(7)8)72(16)39(76)26-70(14)58(83)37-20-18-24-74(37)60(85)43(28(3)4)66-56(45)81/h21-22,27-30,33-34,36-37,42-45,48-49H,17-20,23-26,63H2,1-16H3,(H,65,80)(H,66,81)(H,67,78)(H,68,79)/t33-,34-,36+,37+,42-,43-,44+,45+,48+,49+/m1/s1

InChI Key

RJURFGZVJUQBHK-IIXSONLDSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as cyclic depsipeptides. These are natural or synthetic compounds having sequences of amino and hydroxy carboxylic acid residues (usually α-amino and α-hydroxy acids) connected in a ring. The residues are commonly but not necessarily regliarly alternating. Kingdom

Chemical entities Super Class

Organic compounds Class

Organic acids and derivatives Sub Class

Peptidomimetics Direct Parent

Cyclic depsipeptides Alternative Parents

  • Macrolide lactams
  • Phenoxazines
  • Macrolactams
  • Alpha amino acid esters
  • N-acyl-alpha amino acids and derivatives
  • Benzenoids
  • Dicarboxylic acids and derivatives
  • Primary aromatic amines
  • Vinylogous amides
  • Pyrrolidines
  • Heteroaromatic compounds
  • Tertiary carboxylic acid amides
  • Secondary carboxylic acid amides
  • Lactones
  • Lactams
  • Cyclic ketones
  • Carboxylic acid esters
  • Oxacyclic compounds
  • Azacyclic compounds
  • Organic oxides
  • Hydrocarbon derivatives
  • Organopnictogen compounds

    • Substituents

  • Cyclic depsipeptide
  • Macrolide lactam
  • Phenoxazine
  • Macrolactam
  • Alpha-amino acid ester
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid or derivatives
  • Dicarboxylic acid or derivatives
  • Benzenoid
  • Primary aromatic amine
  • Heteroaromatic compound
  • Vinylogous amide
  • Tertiary carboxylic acid amide
  • Pyrrolidine
  • Amino acid or derivatives
  • Carboxamide group
  • Carboxylic acid ester
  • Lactam
  • Lactone
  • Cyclic ketone
  • Secondary carboxylic acid amide
  • Oxacycle
  • Carboxylic acid derivative
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Organic oxide
  • Organic nitrogen compound
  • Amine
  • Organonitrogen compound
  • Organooxygen compound
  • Primary amine
  • Carbonyl group
  • Organopnictogen compound
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

  • actinomycin (CHEBI:27666 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anti-Bacterial Agents
  • Antibiotics
  • Antibiotics, Antineoplastic
  • Antineoplastic Agents
  • Nucleic Acid Synthesis Inhibitors
  • Protein Synthesis Inhibitors

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point241.5 – 243 °CNot Available Boiling PointNot AvailableNot Available Water Solubility2.00e-02 g/LNot Available LogP1.6Not Available

    Predicted Properties

    Property Value Source Water Solubility0.02 mg/mLALOGPS logP2.76ALOGPS logP-0.097ChemAxon logS-4.8ALOGPS pKa (Strongest Acidic)10.52ChemAxon pKa (Strongest Basic)-0.13ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count16ChemAxon Hydrogen Donor Count5ChemAxon Polar Surface Area355.54 Å2ChemAxon Rotatable Bond Count8ChemAxon Refractivity326.17 m3·mol-1ChemAxon Polarizability129.2 Å3ChemAxon Number of Rings7ChemAxon Bioavailability0ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Not Available Biological Properties Cellliar Locations

  • Cytoplasm
  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00970

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00970

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB00970 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    10482167 KEGG Compound ID

    C06770 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Dactinomycin NuGOwiki Link

    HMDB15105 Metagene Link

    HMDB15105 METLIN ID

    Not Available PubChem Compound

    457193 PDB ID

    Not Available ChEBI ID

    27666

    Product: CZC-25147 (hydrochloride)

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Sobell HM: Actinomycin and DNA transcription. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5328-31. [PubMed:2410919 ]
    2. 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:15543019 ]
    3. 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:16803542 ]
    4. 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:17102824 ]

    Transporters

    General function:
    Involved in ion transmembrane transporter activity
    Specific function:
    Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Also relative uptake activity ratio of carnitine to TEA is 11.3
    Gene Name:
    SLC22A5
    Uniprot ID:
    O76082
    Molecular weight:
    62751.1
    References
    1. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. [PubMed:10525100 ]
    General function:
    Involved in ATP binding
    Specific function:
    Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o- glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency
    Gene Name:
    ABCC1
    Uniprot ID:
    P33527
    Molecular weight:
    171589.5
    References
    1. Breuninger LM, Paul S, Gaughan K, Miki T, Chan A, Aaronson SA, Kruh GD: Expression of multidrug resistance-associated protein in NIH/3T3 cells confers multidrug resistance associated with increased drug efflux and altered intracellular drug distribution. Cancer Res. 1995 Nov 15;55(22):5342-7. [PubMed:7585598 ]
    General function:
    Involved in ATP binding
    Specific function:
    May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Transports glutathione conjugates as leukotriene-c4 (LTC4) and N-ethylmaleimide S-glutathione (NEM-GS)
    Gene Name:
    ABCC6
    Uniprot ID:
    O95255
    Molecular weight:
    164904.8
    References
    1. Belinsky MG, Chen ZS, Shchaveleva I, Zeng H, Kruh GD: Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6). Cancer Res. 2002 Nov 1;62(21):6172-7. [PubMed:12414644 ]
    General function:
    Involved in ATP binding
    Specific function:
    Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
    Gene Name:
    ABCB1
    Uniprot ID:
    P08183
    Molecular weight:
    141477.3
    References
    1. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. [PubMed:11602674 ]
    2. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [PubMed:14985103 ]
    3. Ambudkar SV, Lelong IH, Zhang J, Cardarelli CO, Gottesman MM, Pastan I: Partial purification and reconstitution of the human multidrug-resistance pump: characterization of the drug-stimulatable ATP hydrolysis. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8472-6. [PubMed:1356264 ]
    General function:
    Involved in ATP binding
    Specific function:
    Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123
    Gene Name:
    ABCG2
    Uniprot ID:
    Q9UNQ0
    Molecular weight:
    72313.5
    References
    1. Wang X, Furukawa T, Nitanda T, Okamoto M, Sugimoto Y, Akiyama S, Baba M: Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Mol Pharmacol. 2003 Jan;63(1):65-72. [PubMed:12488537 ]

    PMID: 17975020

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