Identification

Name
Amsacrine
Accession Number
DB00276  (APRD00064)
Type
Small Molecule
Groups
Approved
Description

Aminoacridine derivative that is a potent intercalating antineoplastic agent. It is effective in the treatment of acute leukemias and malignant lymphomas, but has poor activity in the treatment of solid tumors. It is frequently used in combination with other antineoplastic agents in chemotherapy protocols. It produces consistent but acceptable myelosuppression and cardiotoxic effects. [PubChem]

Structure
Thumb
Synonyms
  • 4'-(9-Acridinylamino)-3'-methoxymethanesulfonanilide
  • 4'-(9-Acridinylamino)methanesulfon-m-anisidide
  • 4'-(9-Acridinylamino)methanesulfon-meta-anisidide
  • 4'-(9-Acridinylamino)methanesulphon-m-anisidide
  • Acridinyl anisidide
  • Amsacrine
  • m-AMSA
  • mAMSA
External IDs
CL-880 / NSC-156303 / NSC-249992 / SN-11841 / SN-21429
Product Ingredients
IngredientUNIICASInChI Key
Amsacrine gluconateM4P91439UZ80277-07-2XXNAQBNJPZNRSZ-IFWQJVLJSA-N
Amsacrine hydrochlorideU66HX4K4CO54301-15-4WDISRLXRMMTXEV-UHFFFAOYSA-N
Amsacrine mesylate7LWQ0T63UA54301-16-5KIDGPIWSXHBPDH-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Amsa Pd Inj 50mg/mlLiquid50 mgIntravenousErfa Canada 2012 Inc1983-12-31Not applicableCanada
International/Other Brands
Amekrin / AMSA P-D / Amsidine / Amsidyl
Categories
UNII
00DPD30SOY
CAS number
51264-14-3
Weight
Average: 393.459
Monoisotopic: 393.114712179
Chemical Formula
C21H19N3O3S
InChI Key
XCPGHVQEEXUHNC-UHFFFAOYSA-N
InChI
InChI=1S/C21H19N3O3S/c1-27-20-13-14(24-28(2,25)26)11-12-19(20)23-21-15-7-3-5-9-17(15)22-18-10-6-4-8-16(18)21/h3-13,24H,1-2H3,(H,22,23)
IUPAC Name
N-{4-[(acridin-9-yl)amino]-3-methoxyphenyl}methanesulfonamide
SMILES
COC1=C(NC2=C3C=CC=CC3=NC3=CC=CC=C23)C=CC(NS(C)(=O)=O)=C1

Pharmacology

Indication

For treatment of acute myeloid leukaemia.

Structured Indications
Pharmacodynamics

Amsacrine is an aminoacridine derivative that is a potent intercalating antineoplastic agent. It is effective in the treatment of acute leukemias and malignant lymphomas, but has poor activity in the treatment of solid tumors. It is frequently used in combination with other antineoplastic agents in chemotherapy protocols. It produces consistent but acceptable myelosuppression and cardiotoxic effects.

Mechanism of action

Amsacrine binds to DNA through intercalation and external binding. It has a base specificity for A-T pairs. Rapidly dividing cells are two to four times more sensitive to amsacrine than are resting cells. Amsacrine appears to cleave DNA by inducing double stranded breaks. Amsacrine also targets and inhibits topoisomerase II. Cytotoxicity is greatest during the S phase of the cell cycle when topoisomerase levels are at a maximum.

TargetActionsOrganism
ADNA
intercalation
Human
ADNA topoisomerase 2-alpha
inhibitor
Human
UPotassium voltage-gated channel subfamily H member 2
inhibitor
Human
UAlpha-1-acid glycoprotein 1Not AvailableHuman
USerum albuminNot AvailableHuman
Absorption

Poorly absorbed

Volume of distribution
Not Available
Protein binding

96-98%

Metabolism

Extensive, primarily hepatic, converted to glutathione conjugate.

Route of elimination
Not Available
Half life

8-9 hours

Clearance
Not Available
Toxicity

Symptoms of overdose include nausea and vomiting, diarrhea, some cardiotoxicity (rarely).

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Amsacrine can be increased when it is combined with Abiraterone.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Amsacrine.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Amsacrine.Experimental
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Amsacrine.Approved
AmiodaroneThe metabolism of Amsacrine can be decreased when combined with Amiodarone.Approved, Investigational
ArtemetherThe metabolism of Amsacrine can be decreased when combined with Artemether.Approved
AtomoxetineThe metabolism of Amsacrine can be decreased when combined with Atomoxetine.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Amsacrine.Investigational
BetaxololThe metabolism of Amsacrine can be decreased when combined with Betaxolol.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Amsacrine.Approved, Investigational
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Amsacrine.Approved
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Amsacrine.Approved
BupropionThe metabolism of Amsacrine can be decreased when combined with Bupropion.Approved
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Amsacrine.Approved
CelecoxibThe metabolism of Amsacrine can be decreased when combined with Celecoxib.Approved, Investigational
ChloroquineThe metabolism of Amsacrine can be decreased when combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe metabolism of Amsacrine can be decreased when combined with Chlorpromazine.Approved, Vet Approved
CholecalciferolThe metabolism of Amsacrine can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Amsacrine can be decreased when combined with Cimetidine.Approved
CinacalcetThe metabolism of Amsacrine can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Amsacrine can be decreased when combined with Citalopram.Approved
ClemastineThe metabolism of Amsacrine can be decreased when combined with Clemastine.Approved
ClobazamThe metabolism of Amsacrine can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Amsacrine can be decreased when combined with Clomipramine.Approved, Vet 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 Amsacrine.Approved
ClotrimazoleThe metabolism of Amsacrine can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe risk or severity of adverse effects can be increased when Amsacrine is combined with Clozapine.Approved
CobicistatThe serum concentration of Amsacrine can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Amsacrine can be decreased when combined with Cocaine.Approved, Illicit
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Amsacrine.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 Amsacrine.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Amsacrine.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Amsacrine.Experimental
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Amsacrine.Approved
DarifenacinThe metabolism of Amsacrine can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Amsacrine can be increased when it is combined with Darunavir.Approved
DelavirdineThe metabolism of Amsacrine can be decreased when combined with Delavirdine.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Amsacrine.Approved
DesipramineThe metabolism of Amsacrine can be decreased when combined with Desipramine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Amsacrine.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Amsacrine.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Amsacrine.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Amsacrine.Approved
DiphenhydramineThe metabolism of Amsacrine can be decreased when combined with Diphenhydramine.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Amsacrine.Approved, Investigational
DosulepinThe metabolism of Amsacrine can be decreased when combined with Dosulepin.Approved
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Amsacrine.Approved, Investigational
DronedaroneThe metabolism of Amsacrine can be decreased when combined with Dronedarone.Approved
DuloxetineThe metabolism of Amsacrine can be decreased when combined with Duloxetine.Approved
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Amsacrine.Approved
EliglustatThe metabolism of Amsacrine can be decreased when combined with Eliglustat.Approved
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Amsacrine.Approved
FingolimodAmsacrine may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
FluoxetineThe metabolism of Amsacrine can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe metabolism of Amsacrine can be decreased when combined with Fluvoxamine.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Amsacrine.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Amsacrine.Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Amsacrine.Experimental
HaloperidolThe metabolism of Amsacrine can be decreased when combined with Haloperidol.Approved
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Amsacrine.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Amsacrine.Approved, Withdrawn
ImipramineThe metabolism of Amsacrine can be decreased when combined with Imipramine.Approved
IndinavirThe metabolism of Amsacrine can be decreased when combined with Indinavir.Approved
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Amsacrine.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Amsacrine.Investigational
IsoniazidThe metabolism of Amsacrine can be decreased when combined with Isoniazid.Approved
KetoconazoleThe metabolism of Amsacrine can be decreased when combined with Ketoconazole.Approved, Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Amsacrine.Experimental
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Amsacrine.Approved
LeflunomideThe risk or severity of adverse effects can be increased when Amsacrine is combined with Leflunomide.Approved, Investigational
LopinavirThe metabolism of Amsacrine can be decreased when combined with Lopinavir.Approved
LorcaserinThe metabolism of Amsacrine can be decreased when combined with Lorcaserin.Approved
LumefantrineThe metabolism of Amsacrine can be decreased when combined with Lumefantrine.Approved
ManidipineThe metabolism of Amsacrine can be decreased when combined with Manidipine.Approved, Investigational
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Amsacrine.Investigational, Withdrawn
MethadoneThe metabolism of Amsacrine can be decreased when combined with Methadone.Approved
MethotrimeprazineThe metabolism of Amsacrine can be decreased when combined with Methotrimeprazine.Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Amsacrine.Experimental
MetoprololThe metabolism of Amsacrine can be decreased when combined with Metoprolol.Approved, Investigational
MidostaurinThe metabolism of Amsacrine can be decreased when combined with Midostaurin.Approved
MirabegronThe metabolism of Amsacrine can be decreased when combined with Mirabegron.Approved
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Amsacrine.Approved
NatalizumabThe risk or severity of adverse effects can be increased when Amsacrine is combined with Natalizumab.Approved, Investigational
NevirapineThe metabolism of Amsacrine can be decreased when combined with Nevirapine.Approved
NicardipineThe metabolism of Amsacrine can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Amsacrine can be decreased when combined with Nilotinib.Approved, Investigational
OleandrinOleandrin may decrease the cardiotoxic activities of Amsacrine.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Amsacrine.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Amsacrine.Approved, Vet Approved
PanobinostatThe serum concentration of Amsacrine can be increased when it is combined with Panobinostat.Approved, Investigational
ParoxetineThe metabolism of Amsacrine can be decreased when combined with Paroxetine.Approved, Investigational
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Amsacrine.Approved
Peginterferon alfa-2bThe serum concentration of Amsacrine can be decreased when it is combined with Peginterferon alfa-2b.Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Amsacrine.Experimental
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Amsacrine.Approved, Investigational
PromazineThe metabolism of Amsacrine can be decreased when combined with Promazine.Approved, Vet Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Amsacrine.Experimental
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Amsacrine.Approved
QuinidineThe metabolism of Amsacrine can be decreased when combined with Quinidine.Approved
QuinineThe metabolism of Amsacrine can be decreased when combined with Quinine.Approved
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Amsacrine 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 Amsacrine.Approved
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Amsacrine.Approved, Investigational
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Amsacrine.Approved, Investigational
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Amsacrine.Investigational
RitonavirThe metabolism of Amsacrine can be decreased when combined with Ritonavir.Approved, Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Amsacrine.Approved
RolapitantThe metabolism of Amsacrine can be decreased when combined with Rolapitant.Approved
RopiniroleThe metabolism of Amsacrine can be decreased when combined with Ropinirole.Approved, Investigational
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Amsacrine.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Amsacrine.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Amsacrine.Approved
SertralineThe metabolism of Amsacrine can be decreased when combined with Sertraline.Approved
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Amsacrine.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Amsacrine.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Amsacrine.Investigational
StiripentolThe metabolism of Amsacrine can be decreased when combined with Stiripentol.Approved
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Amsacrine.Approved, Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Amsacrine.Investigational
TerbinafineThe metabolism of Amsacrine can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Amsacrine.Investigational
ThioridazineThe metabolism of Amsacrine can be decreased when combined with Thioridazine.Approved, Withdrawn
TiclopidineThe metabolism of Amsacrine can be decreased when combined with Ticlopidine.Approved
TipranavirThe metabolism of Amsacrine can be decreased when combined with Tipranavir.Approved, Investigational
TofacitinibAmsacrine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Amsacrine.Approved, Investigational
TranylcypromineThe metabolism of Amsacrine can be decreased when combined with Tranylcypromine.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Amsacrine.Approved, Investigational
VenlafaxineThe metabolism of Amsacrine can be decreased when combined with Venlafaxine.Approved
VincristineThe serum concentration of Vincristine can be increased when it is combined with Amsacrine.Approved, Investigational
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Amsacrine.Approved
ZiprasidoneThe metabolism of Amsacrine can be decreased when combined with Ziprasidone.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Amsacrine.Approved
Food Interactions
Not Available

References

General References
  1. Link [Link]
External Links
Human Metabolome Database
HMDB14421
KEGG Drug
D02321
KEGG Compound
C01553
PubChem Compound
2179
PubChem Substance
46507539
ChemSpider
2094
BindingDB
87351
ChEBI
2687
ChEMBL
CHEMBL43
Therapeutic Targets Database
DAP000046
PharmGKB
PA10309
HET
ASW
Wikipedia
Amsacrine
ATC Codes
L01XX01 — Amsacrine
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
4g0u
MSDS
Download (48.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentLeukemias1
2, 3RecruitingTreatmentLeukemias1
3CompletedTreatmentLeukemias1
3CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
3CompletedTreatmentLeukemias / Neutropenias1
3Unknown StatusTreatmentLeukemias / Neutropenias1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
LiquidIntravenous50 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)235 °CPhysProp
water solubility<1 mg/mLNot Available
logP3.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00317 mg/mLALOGPS
logP4.66ALOGPS
logP3.16ChemAxon
logS-5.1ALOGPS
pKa (Strongest Acidic)10.82ChemAxon
pKa (Strongest Basic)8.44ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area80.32 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity107.69 m3·mol-1ChemAxon
Polarizability41.65 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.667
Caco-2 permeable+0.5
P-glycoprotein substrateNon-substrate0.766
P-glycoprotein inhibitor INon-inhibitor0.5625
P-glycoprotein inhibitor IINon-inhibitor0.7178
Renal organic cation transporterNon-inhibitor0.8983
CYP450 2C9 substrateNon-substrate0.7427
CYP450 2D6 substrateNon-substrate0.8266
CYP450 3A4 substrateNon-substrate0.5159
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9232
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9051
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.8098
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.2509 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7711
hERG inhibition (predictor II)Inhibitor0.7355
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 acridines. These are organic compounds containing the acridine moiety, a linear tricyclic heterocycle which consists of two benzene rings joined by a pyridine ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Benzoquinolines
Direct Parent
Acridines
Alternative Parents
4-aminoquinolines / Sulfanilides / Aminophenyl ethers / Methoxyanilines / Phenoxy compounds / Methoxybenzenes / Anisoles / Alkyl aryl ethers / Aminopyridines and derivatives / Organosulfonamides
show 8 more
Substituents
Acridine / 4-aminoquinoline / Aminoquinoline / Sulfanilide / Aminophenyl ether / Methoxyaniline / Phenoxy compound / Anisole / Phenol ether / Methoxybenzene
show 26 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
aromatic ether, sulfonamide, acridines (CHEBI:2687)

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Intercalation
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. Gabelica V, Rosu F, De Pauw E, Antoine R, Tabarin T, Broyer M, Dugourd P: Electron photodetachment dissociation of DNA anions with covalently or noncovalently bound chromophores. J Am Soc Mass Spectrom. 2007 Nov;18(11):1990-2000. Epub 2007 Aug 22. [PubMed:17900923]
  4. Capranico G, Guano F, Moro S, Zagotto G, Sissi C, Gatto B, Zunino F, Menta E, Palumbo M: Mapping drug interactions at the covalent topoisomerase II-DNA complex by bisantrene/amsacrine congeners. J Biol Chem. 1998 May 22;273(21):12732-9. [PubMed:9582297]
Details
2. DNA topoisomerase 2-alpha
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
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...
Gene Name
TOP2A
Uniprot ID
P11388
Uniprot Name
DNA topoisomerase 2-alpha
Molecular Weight
174383.88 Da
References
  1. Finlay GJ, Atwell GJ, Baguley BC: Inhibition of the action of the topoisomerase II poison amsacrine by simple aniline derivatives: evidence for drug-protein interactions. Oncol Res. 1999;11(6):249-54. [PubMed:10691026]
  2. Ferlin MG, Marzano C, Chiarelotto G, Baccichetti F, Bordin F: Synthesis and antiproliferative activity of some variously substituted acridine and azacridine derivatives. Eur J Med Chem. 2000 Sep;35(9):827-37. [PubMed:11006484]
  3. Matsumoto Y, Takano H, Kunishio K, Nagao S, Fojo T: Hypophosphorylation of topoisomerase IIalpha in etoposide (VP-16)-resistant human carcinoma cell lines associated with carboxy-terminal truncation. Jpn J Cancer Res. 2001 Jul;92(7):799-805. [PubMed:11473732]
  4. Lee MS, Wang JC, Beran M: Two independent amsacrine-resistant human myeloid leukemia cell lines share an identical point mutation in the 170 kDa form of human topoisomerase II. J Mol Biol. 1992 Feb 20;223(4):837-43. [PubMed:1311390]
  5. Nitiss JL, Liu YX, Harbury P, Jannatipour M, Wasserman R, Wang JC: Amsacrine and etoposide hypersensitivity of yeast cells overexpressing DNA topoisomerase II. Cancer Res. 1992 Aug 15;52(16):4467-72. [PubMed:1322791]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  7. Arimondo P, Boukarim C, Bailly C, Dauzonne D, Monneret C: Design of two etoposide-amsacrine conjugates: topoisomerase II and tubuline polymerization inhibition and relation to cytotoxicity. Anticancer Drug Des. 2000 Dec;15(6):413-21. [PubMed:11716434]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
References
  1. Thomas D, Hammerling BC, Wu K, Wimmer AB, Ficker EK, Kirsch GE, Kochan MC, Wible BA, Scholz EP, Zitron E, Kathofer S, Kreye VA, Katus HA, Schoels W, Karle CA, Kiehn J: Inhibition of cardiac HERG currents by the DNA topoisomerase II inhibitor amsacrine: mode of action. Br J Pharmacol. 2004 Jun;142(3):485-94. Epub 2004 May 17. [PubMed:15148258]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Finlay GJ, Baguley BC: Effects of protein binding on the in vitro activity of antitumour acridine derivatives and related anticancer drugs. Cancer Chemother Pharmacol. 2000;45(5):417-22. [PubMed:10803926]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Finlay GJ, Baguley BC: Effects of protein binding on the in vitro activity of antitumour acridine derivatives and related anticancer drugs. Cancer Chemother Pharmacol. 2000;45(5):417-22. [PubMed:10803926]

Enzymes

Details
1. Cytochrome P450 2D6
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
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. 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]

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