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

Stem definitionDrug idCAS RN
acridine derivatives 203 51264-14-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • amsacrine
  • acridinylanisidide
  • amekrin
  • amsidil
  • amsidine
  • amsidyl
  • lamasine
An aminoacridine derivative that intercalates into DNA and is used as an antineoplastic agent.
  • Molecular weight: 393.46
  • Formula: C21H19N3O3S
  • CLOGP: 4.54
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 2
  • TPSA: 80.32
  • ALOGS: -5.09
  • ROTB: 4

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 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) 10.05 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution) 1.60 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 4.30 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.03 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 4.70 hours Lombardo F, Berellini G, Obach RS
BA (Bioavailability) 0 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.329 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 2.193 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 39.174 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 11.455 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 1.400 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 5.300 % High 1
herg hERG pIC50 5.310 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 12.794 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 34.119 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.850 % High 1
kinase-safety-class ACVR2A,ACVR2B,AKT2,AKT3,ALK,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK1,CDK5,CDK9,CHEK1,CSF1R,DDR1,DYRK1B,EGFR,EIF2AK3,EPHA2,EPHB4,ERBB2,FLT3,GRK2,GSK3B,ITK,JAK1,JAK2,KIT,MAP2K6,MAP3K1,MAP3K10,MAP3K11,MAP3K21,MAP3K7,MAP4K1,MAP4K3,MAPK10,MAPK7,MAPK9,MAPKAPK2,MARK4,MET,MTOR,NTRK2,PDK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PIM2,PRKCD,PRKDC,SGK1,SIK2,SIK3,STK33,SYK,TEK,TTK,ULK1,ULK2 65
kinase-selectivity-class AAK1,ACVR2A,ACVR2B,ALK,AURKA,AXL,BRAF,CAMK2D,CDK9,DDR1,DYRK1B,ERBB2,FLT3,GRK2,JAK1,MAP2K3,MAP2K6,MAP3K10,MAP3K21,MAP4K1,MAPK7,MAPK8,MARK4,PDK4,SIK2,SIK3,STK33,TTK,ULK1 29
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 10.666 High 1
mh-clint Mouse hepatocyte intrinsic clearance 46.559 High 1
mppb Mouse plasma protein binding (% unbound) 1.640 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 17.140 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 3.270 % High 1
rh-clint Rat hepatocyte intrinsic clearance 60.674 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 16.250 % High 1
rppb Rat plasma protein binding (% unbound) 1.030 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 1.102 uM High 1

Approvals:

DateAgencyCompanyOrphan
Jan. 1, 1987 YEAR INTRODUCED

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
Systemic inflammatory response syndrome 109.05 85.03 22 783 6494 90621148
Graft versus host disease 92.76 85.03 20 785 8124 90619518
Acute myeloid leukaemia recurrent 85.82 85.03 15 790 2042 90625600

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
Acute myeloid leukaemia recurrent 115.71 97.58 23 661 3489 42617162

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
Acute myeloid leukaemia recurrent 159.69 80.42 31 1409 5108 110582751
Venoocclusive liver disease 157.20 80.42 37 1403 15170 110572689
Drug resistance 133.39 80.42 43 1397 56331 110531528
Graft versus host disease in gastrointestinal tract 109.49 80.42 25 1415 8943 110578916
Dysbiosis 105.20 80.42 19 1421 2113 110585746
Graft versus host disease 100.47 80.42 27 1413 18779 110569080
Systemic inflammatory response syndrome 85.34 80.42 22 1418 13021 110574838

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01XX01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Other antineoplastic agents
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50750 EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor
MeSH PA D000970 Antineoplastic Agents
MeSH PA D007202 Indicators and Reagents
MeSH PA D007364 Intercalating Agents

Related Drugs by ATC class:

L01XX Other antineoplastic agents 33 drugs
adagrasibafliberceptaltretamineanagrelidearsenic trioxideasparaginasebelzutifancalaspargase pegolcelecoxibdarinaparsindenileukin diftitoxeflornithine show all 33 →

Drug Use | Suggest Off label Use Form| |View source of the data|

None




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.98 acidic
pKa2 8.25 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
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 6.68 CHEMBL
Cytochrome P450 2D6 Enzyme Ki 5.12 WOMBAT-PK
DNA topoisomerase 2-alpha Enzyme IC50 5 CHEMBL
DNA topoisomerase I, mitochondrial Enzyme IC50 7.43 WOMBAT-PK
DNA topoisomerase 1 Enzyme IC50 7.43 WOMBAT-PK
DNA topoisomerase 2-beta Enzyme EC50 4.96 CHEMBL
Solute carrier family 22 member 1 Transporter IC50 5.30 CHEMBL
Lysine-specific histone demethylase 1A Enzyme IC50 6.06 CHEMBL
DNA topoisomerase II Enzyme EC50 6.14 CHEMBL

External reference:

IDSource
4025233 VUID
N0000171765 NUI
D02321 KEGG_DRUG
151347 RXNORM
C0002699 UMLSCUI
CHEBI:2687 CHEBI
ASW PDB_CHEM_ID
CHEMBL43 ChEMBL_ID
D000677 MESH_DESCRIPTOR_UI
DB00276 DRUGBANK_ID
2179 PUBCHEM_CID
4864 INN_ID
00DPD30SOY UNII
4025233 VANDF
003469 NDDF
326955000 SNOMEDCT_US
391774005 SNOMEDCT_US
00DPD30SOY INXIGHT DRUGS

Pharmaceutical products:

None