Identification

Name
Dactinomycin
Accession Number
DB00970  (APRD00124)
Type
Small Molecule
Groups
Approved
Description

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)

Structure
Thumb
Synonyms
  • 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-dicarboxamide
  • ActD
  • Actinomycin C1
  • Actinomycin D
  • Actinomycin iv
  • Dactinomicina
  • Dactinomycin
  • Dactinomycine
  • Dactinomycinum
  • Meractinomycin
External IDs
NCI-C04682 / NSC-3053
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CosmegenInjection, powder, lyophilized, for solution.5 mg/mLIntravenousRecordati Rare Diseases Inc1964-12-10Not applicableUs
CosmegenPowder, for solution0.5 mgIntravenousRecordati Rare Diseases Inc1963-12-31Not applicableCanada
International/Other Brands
Lyovac Cosmegen (Lundbeck)
Categories
UNII
1CC1JFE158
CAS number
50-76-0
Weight
Average: 1255.417
Monoisotopic: 1254.628474764
Chemical Formula
C62H86N12O16
InChI Key
RJURFGZVJUQBHK-IIXSONLDSA-N
InChI
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
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
SMILES
[H][[email protected]@]12CCCN1C(=O)[[email protected]](NC(=O)[[email protected]@H](NC(=O)C1=C3N=C4C(OC3=C(C)C=C1)=C(C)C(=O)C(N)=C4C(=O)N[[email protected]]1[[email protected]@H](C)OC(=O)[[email protected]](C(C)C)N(C)C(=O)CN(C)C(=O)[[email protected]]3([H])CCCN3C(=O)[[email protected]](NC1=O)C(C)C)[[email protected]@H](C)OC(=O)[[email protected]](C(C)C)N(C)C(=O)CN(C)C2=O)C(C)C

Pharmacology

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

Structured Indications
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.

TargetActionsOrganism
ADNA
adduct
Human
UDNA topoisomerase 2Not AvailableHomo sapiens
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Dactinomycin.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Dactinomycin.Experimental
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Dactinomycin.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Dactinomycin.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Dactinomycin.Approved, Investigational
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Dactinomycin.Approved
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Dactinomycin.Approved
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Dactinomycin.Approved
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Dactinomycin.Approved
ClozapineThe risk or severity of adverse effects can be increased when Dactinomycin is combined with Clozapine.Approved
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Dactinomycin.Approved
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Dactinomycin.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Dactinomycin.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Dactinomycin.Experimental
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Dactinomycin.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Dactinomycin.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Dactinomycin.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Dactinomycin.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Dactinomycin.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Dactinomycin.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Dactinomycin.Approved, Investigational
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Dactinomycin.Approved, Investigational
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Dactinomycin.Approved
EltrombopagThe serum concentration of Dactinomycin can be increased when it is combined with Eltrombopag.Approved
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Dactinomycin.Approved
FingolimodDactinomycin may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Dactinomycin.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Dactinomycin.Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Dactinomycin.Experimental
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Dactinomycin.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Dactinomycin.Approved, Withdrawn
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Dactinomycin.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Dactinomycin.Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Dactinomycin.Experimental
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Dactinomycin.Approved
LeflunomideThe risk or severity of adverse effects can be increased when Dactinomycin is combined with Leflunomide.Approved, Investigational
LumacaftorThe serum concentration of Dactinomycin can be decreased when it is combined with Lumacaftor.Approved
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Dactinomycin.Investigational, Withdrawn
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Dactinomycin.Experimental
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Dactinomycin.Approved
NatalizumabThe risk or severity of adverse effects can be increased when Dactinomycin is combined with Natalizumab.Approved, Investigational
OleandrinOleandrin may decrease the cardiotoxic activities of Dactinomycin.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Dactinomycin.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Dactinomycin.Approved, Vet Approved
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Dactinomycin.Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Dactinomycin.Experimental
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Dactinomycin.Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Dactinomycin.Approved, Investigational
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Dactinomycin.Experimental
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Dactinomycin.Approved
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Dactinomycin is combined with Rabies virus inactivated antigen, A.Approved
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Dactinomycin.Approved
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Dactinomycin.Approved, Investigational
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Dactinomycin.Approved, Investigational
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Dactinomycin.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Dactinomycin.Approved
RolapitantThe serum concentration of Dactinomycin can be increased when it is combined with Rolapitant.Approved
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Dactinomycin.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Dactinomycin.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Dactinomycin.Approved
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Dactinomycin.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Dactinomycin.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Dactinomycin.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Dactinomycin.Approved, Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Dactinomycin.Investigational
TeriflunomideThe serum concentration of Dactinomycin can be increased when it is combined with Teriflunomide.Approved
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Dactinomycin.Investigational
TofacitinibDactinomycin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Dactinomycin.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Dactinomycin.Approved, Investigational
VincristineThe serum concentration of Vincristine can be increased when it is combined with Dactinomycin.Approved, Investigational
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Dactinomycin.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Dactinomycin.Approved
Food Interactions
Not Available

References

Synthesis Reference

Waksman, S.A. and Woodruff, H.B.; US. Patent 2,378,876; June 19,1945; assigned to Merck & Co., Inc.

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. 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]
  3. 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]
  4. 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]
External Links
Human Metabolome Database
HMDB15105
KEGG Drug
D00214
KEGG Compound
C06770
PubChem Compound
457193
PubChem Substance
46509192
ChemSpider
10482167
BindingDB
50089528
ChEBI
27666
ChEMBL
CHEMBL1554
Therapeutic Targets Database
DNC000380
PharmGKB
PA151917012
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Dactinomycin
ATC Codes
L01DA01 — Dactinomycin
AHFS Codes
  • 10:00.00 — Antineoplastic Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2WithdrawnTreatmentMelanoma1
2CompletedTreatmentAdult Rhabdomyosarcoma / Childhood Alveolar Rhabdomyosarcoma / Childhood Embryonal Rhabdomyosarcoma / Metastatic Childhood Soft Tissue Sarcoma / Stage IV Adult Soft Tissue Sarcoma / Untreated Childhood Rhabdomyosarcoma1
2CompletedTreatmentCancer, Ovarian / Extragonadal Germ Cell Tumor1
2CompletedTreatmentCancer, Ovarian / Sarcomas / Small Intestine Cancer1
2CompletedTreatmentCentral Nervous System Tumor, Pediatric1
2CompletedTreatmentChildhood Renal Cell Carcinoma / Clear Cell Renal Cell Carcinoma / Clear Cell Sarcoma of the Kidney / Papillary Renal Cell Carcinoma / Rhabdoid Tumors of the Kidney (RTK) / Stage I Renal Cell Cancer / Stage I Renal Wilms Tumor / Stage II Renal Cell Cancer / Stage II Renal Wilms Tumor / Stage III Renal Cell Cancer / Stage III Renal Wilms Tumor / Stage IV Renal Cell Cancer / Stage IV Renal Wilms Tumor1
2CompletedTreatmentGestational Trophoblastic Disease1
2CompletedTreatmentMelanoma (Skin) / Sarcomas1
2CompletedTreatmentSarcomas1
2RecruitingTreatmentMelanoma1
2RecruitingTreatmentRhabdomyosarcomas1
2TerminatedTreatmentSarcomas1
2Unknown StatusTreatmentRenal Cancers1
2Unknown StatusTreatmentSarcomas2
3Active Not RecruitingTreatmentAdult Malignant Mesenchymoma / Adult Rhabdomyosarcoma / Childhood Alveolar Rhabdomyosarcoma / Childhood Botryoid-Type Embryonal Rhabdomyosarcoma / Childhood Embryonal Rhabdomyosarcoma / Childhood Malignant Mesenchymoma / Non-Metastatic Childhood Soft Tissue Sarcoma / Stage I Adult Soft Tissue Sarcoma / Stage II Adult Soft Tissue Sarcoma / Stage III Adult Soft Tissue Sarcoma / Untreated Childhood Rhabdomyosarcoma1
3Active Not RecruitingTreatmentAdult Renal Wilms Tumor / Beckwith-Wiedemann Syndrome / Childhood Renal Wilms Tumor / Diffuse Hyperplastic Perilobar Nephroblastomatosis / Hemihypertrophy / Stage I Renal Wilms Tumor / Stage II Renal Wilms Tumor / Stage III Renal Wilms Tumor / Stage IV Renal Wilms Tumor / Stage V Renal Wilms Tumor1
3Active Not RecruitingTreatmentAdult Rhabdomyosarcoma / Embryonal Childhood Rhabdomyosarcoma / Embryonal-botryoid Childhood Rhabdomyosarcoma / Previously Untreated Childhood Rhabdomyosarcoma1
3Active Not RecruitingTreatmentChoriocarcinoma / FIGO Stage I Gestational Trophoblastic Tumor / FIGO Stage II Gestational Trophoblastic Tumor / FIGO Stage III Gestational Trophoblastic Tumor / Hydatidiform Mole1
3Active Not RecruitingTreatmentSarcomas1
3Active Not RecruitingTreatmentStage III Wilms Tumor With Loss of Heterozygosity (LOH) for 1p and 16q / Stage IV Wilms Tumor1
3CompletedTreatmentAdult Malignant Mesenchymoma / Adult Rhabdomyosarcoma / Alveolar Childhood Rhabdomyosarcoma / Childhood Malignant Mesenchymoma / Embryonal Childhood Rhabdomyosarcoma / Embryonal-botryoid Childhood Rhabdomyosarcoma / Nonmetastatic Childhood Soft Tissue Sarcoma / Previously Untreated Childhood Rhabdomyosarcoma / Stage I Adult Soft Tissue Sarcoma / Stage II Adult Soft Tissue Sarcoma / Stage III Adult Soft Tissue Sarcoma1
3CompletedTreatmentChildhood Malignant Fibrous Histiocytoma of Bone / Sarcomas1
3CompletedTreatmentGood Prognosis Metastatic Gestational Trophoblastic Tumor / Hydatidiform Mole / Non-Metastatic Gestational Trophoblastic Tumor / Uterine Corpus Choriocarcinoma1
3CompletedTreatmentLeukemias / Malignant Lymphomas1
3CompletedTreatmentRenal Cancers2
3CompletedTreatmentSarcomas1
3CompletedTreatmentStage I Wilms Tumor / Stage II Wilms Tumor / Stage III Wilms Tumor1
3Not Yet RecruitingTreatmentGestational Trophoblastic Neoplasms1
3RecruitingTreatmentEwing's Sarcoma (ES)1
3SuspendedTreatmentBotryoid-Type Embryonal Rhabdomyosarcoma / Rhabdomyosarcoma, Alveolar / Rhabdomyosarcoma, Embryonal / Rhabdomyosarcomas / Sclerosing Rhabdomyosarcoma / Spindle Cell Rhabdomyosarcoma / Untreated Childhood Rhabdomyosarcoma1
3SuspendedTreatmentBrain Cancer / Choroid Plexus Tumors1
3Unknown StatusTreatmentRenal Cancers2
3Unknown StatusTreatmentSarcomas3
Not AvailableRecruitingTreatmentPleuropulmonary Blastoma1

Pharmacoeconomics

Manufacturers
  • Lundbeck inc
  • Bedford laboratories div ben venue laboratories inc
Packagers
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous.5 mg/mL
Powder, for solutionIntravenous0.5 mg
Prices
Unit descriptionCostUnit
Cosmegen 0.5 mg vial684.36USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)241.5-243 °CNot Available
water solubilitySoluble at 10 °CNot Available
logP1.6Not Available
Predicted Properties
PropertyValueSource
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
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7619
Blood Brain Barrier-0.9659
Caco-2 permeable-0.6568
P-glycoprotein substrateSubstrate0.8368
P-glycoprotein inhibitor INon-inhibitor0.6482
P-glycoprotein inhibitor IINon-inhibitor0.8638
Renal organic cation transporterNon-inhibitor0.8178
CYP450 2C9 substrateNon-substrate0.8589
CYP450 2D6 substrateNon-substrate0.8535
CYP450 3A4 substrateSubstrate0.759
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8614
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8681
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9019
BiodegradationNot ready biodegradable0.983
Rat acute toxicity4.3767 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9208
hERG inhibition (predictor II)Non-inhibitor0.5171
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds 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 regularly alternating.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Peptidomimetics
Sub Class
Depsipeptides
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 / Pyrrolidines / Heteroaromatic compounds / Tertiary carboxylic acid amides
show 12 more
Substituents
Cyclic depsipeptide / Macrolide lactam / Phenoxazine / Alpha-amino acid ester / Macrolactam / N-acyl-alpha amino acid or derivatives / Alpha-amino acid or derivatives / Dicarboxylic acid or derivatives / Benzenoid / Heteroaromatic compound
show 25 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
actinomycin (CHEBI:27666)

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Adduct
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Yang XL, Wang AH: Structural studies of atom-specific anticancer drugs acting on DNA. Pharmacol Ther. 1999 Sep;83(3):181-215. [PubMed:10576292]
  4. Sobell HM: Actinomycin and DNA transcription. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5328-31. [PubMed:2410919]
  5. Hudson JS, Brooks SC, Graves DE: Interactions of actinomycin D with human telomeric G-quadruplex DNA. Biochemistry. 2009 Jun 2;48(21):4440-7. doi: 10.1021/bi900203z. [PubMed:19348506]
Kind
Protein group
Organism
Homo sapiens
Pharmacological action
Unknown
General Function
Ubiquitin binding
Specific Function
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segr...

Components:
References
  1. Felix CA, Hosler MR, Winick NJ, Masterson M, Wilson AE, Lange BJ: ALL-1 gene rearrangements in DNA topoisomerase II inhibitor-related leukemia in children. Blood. 1995 Jun 1;85(11):3250-6. [PubMed:7756657]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Symporter 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 cat...
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Solute carrier family 22 member 5
Molecular Weight
62751.08 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Transporter activity
Specific Function
Isoform 1: May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Transports glutathione conjugates as leukotriene-c4 (LTC4...
Gene Name
ABCC6
Uniprot ID
O95255
Uniprot Name
Multidrug resistance-associated protein 6
Molecular Weight
164904.81 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Transporter activity
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, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
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]

Drug created on June 13, 2005 07:24 / Updated on November 19, 2017 20:33