Details of the Drug

General Information of Drug (ID: DMZKYIV)

Drug Name
Amsacrine
Synonyms
Acridinylanisidide; Amecrin; Amekrin; Amsacrina; Amsacrinum; Amsidine; Amsidyl; Amsine; Lamasine; MAMSA; NAMSA; Acridinyl Anisidide; SN 21429; SN11841; AMSA P-D; Acridinyl anisidide (TN); Amsacrina [INN-Spanish]; Amsacrinum [INN-Latin]; Amsidyl (TN); Cain's Acridine; M-AMSA; Meta-AMSA; Meta-Amsacrine; SN-11841; Amsacrine (USAN/INN); Amsacrine [USAN:BAN:INN]; M-AMSA (TN); N-[4-(9-Acridinylamino)-3-methoxyphenyl]methanesulfonamide; N-(4-(9-Acridinylamino)-3-methoxyphenyl)methanesulfonamide; N-[4-(9-Acridinylamino)-3-methoxy-phenyl]methanesulfonamide; N-[4-(acridin-9-ylamino)-3-methoxyphenyl]methanesulfonamide; N-[4-(acridin-9-ylmethyl)-3-methoxyphenyl]methanesulfonamide; N-(4-(Acridin-9-ylamino)-3-methoxyphenyl)methanesulfonamide; N-[4-(Acridin-9-ylamino)-3-(methyloxy)phenyl]methanesulfonamide; N-[4-(acridin-9-ylamino)-3-(methyloxy)phenyl]methanesulfonamide; 4'-(9-Acridinylamino)-3'-methoxymethanesulfonanilide; 4'-(9-Acridinylamino)methanesulfon-m-anisidide; 4'-(9-Acridinylamino)methanesulfon-meta-anisidide; 4'-(9-Acridinylamino)methanesulphon-m-anisidide
Indication
Disease Entry ICD 11 Status REF
Acute lymphoblastic leukaemia 2A85 Approved [1]
Therapeutic Class
Anticancer Agents
Affected Organisms
Humans and other mammals
ATC Code
L01XX01: Amsacrine
L01XX: Other antineoplastic agents
L01X: OTHER ANTINEOPLASTIC AGENTS
L01: ANTINEOPLASTIC AGENTS
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 393.5
Logarithm of the Partition Coefficient (xlogp) 4
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 6
ADMET Property
Absorption
The drug is poorly absorbed []
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
Clearance
The drug present in the plasma can be removed from the body at the rate of 4.3 mL/min/kg [3]
Elimination
10% of drug is excreted from urine in the unchanged form [2]
Half-life
The concentration or amount of drug in body reduced by one-half in 8 - 9 hours [3]
Metabolism
The drug is metabolized via the hepatic []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 10.05 micromolar/kg/day [4]
Unbound Fraction
The unbound fraction of drug in plasma is 0.029% [3]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.6 L/kg [3]
Chemical Identifiers
Formula
C21H19N3O3S
IUPAC Name
N-[4-(acridin-9-ylamino)-3-methoxyphenyl]methanesulfonamide
Canonical SMILES
COC1=C(C=CC(=C1)NS(=O)(=O)C)NC2=C3C=CC=CC3=NC4=CC=CC=C42
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)
InChIKey
XCPGHVQEEXUHNC-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
2179
ChEBI ID
CHEMBL43
CAS Number
51264-14-3
UNII
00DPD30SOY
DrugBank ID
DB00276
TTD ID
D0G9YH
VARIDT ID
DR00917
INTEDE ID
DR0109
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
DNA topoisomerase II (TOP2) TT0IHXV TOP2A_HUMAN ; TOP2B_HUMAN Inhibitor [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 2D6 (CYP2D6)
Main DME 		DECB0K3 CP2D6_HUMAN Substrate [6]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Albumin (ALB) OTVMM513 ALBU_HUMAN Protein Interaction/Cellular Processes [7]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Gene/Protein Processing [8]
Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN OT81JS6K WRN_HUMAN Drug Response [9]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Post-Translational Modifications [8]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) OTUYHB84 MLP3B_HUMAN Gene/Protein Processing [8]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Post-Translational Modifications [8]
Mitogen-activated protein kinase 12 (MAPK12) OTTCKE27 MK12_HUMAN Gene/Protein Processing [10]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Post-Translational Modifications [8]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Gene/Protein Processing [11]
Protein regulator of cytokinesis 1 (PRC1) OTHD0XS0 PRC1_HUMAN Gene/Protein Processing [12]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 Identification of FDA-approved drugs and bioactives that protect hair cells in the zebrafish (Danio rerio) lateral line and mouse (Mus musculus) ut... J Assoc Res Otolaryngol. 2009 Jun;10(2):191-203.
2 BDDCS applied to over 900 drugs
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
5 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.
6 Phase I pharmacokinetic study of the novel antitumor agent SR233377. Clin Cancer Res. 2000 Aug;6(8):3088-94.
7 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. doi: 10.1007/s002800051011.
8 Amsacrine downregulates BCL2L1 expression and triggers apoptosis in human chronic myeloid leukemia cells through the SIDT2/NOX4/ERK/HuR pathway. Toxicol Appl Pharmacol. 2023 Sep 1;474:116625. doi: 10.1016/j.taap.2023.116625. Epub 2023 Jul 13.
9 Werner's syndrome lymphoblastoid cells are hypersensitive to topoisomerase II inhibitors in the G2 phase of the cell cycle. Mutat Res. 2000 Mar 20;459(2):123-33. doi: 10.1016/s0921-8777(99)00065-8.
10 Phosphorylation and stabilization of topoisomerase II protein by p38 mitogen-activated protein kinase sensitize breast cancer cells to its poisons. J Biol Chem. 2011 Oct 14;286(41):35883-35890. doi: 10.1074/jbc.M111.229260. Epub 2011 Aug 30.
11 Suppression of c-myc expression and c-Myc function in response to sustained DNA damage in MCF-7 breast tumor cells. Biochem Pharmacol. 2001 Sep 1;62(5):593-602. doi: 10.1016/s0006-2952(01)00699-2.
12 Characterization of DNA reactive and non-DNA reactive anticancer drugs by gene expression profiling. Mutat Res. 2007 Jun 1;619(1-2):16-29. doi: 10.1016/j.mrfmmm.2006.12.007. Epub 2007 Feb 8.