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
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]
Adverse Drug Reaction (ADR)
ADR Term Variation Related DOT DOT ID REF
Cytogenetic investigations Not Available TOP1 OT51O0CF [5]
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
CHEBI:2687
CAS Number
51264-14-3
DrugBank ID
DB00276
TTD ID
D0G9YH
VARIDT ID
DR00917
INTEDE ID
DR0109
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 [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 2D6 (CYP2D6)
Main DME
DECB0K3 CP2D6_HUMAN Substrate [7]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Albumin (ALB) OTVMM513 ALBU_HUMAN Protein Interaction/Cellular Processes [8]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Drug Response [9]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Drug Response [10]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Gene/Protein Processing [11]
Beclin-1 (BECN1) OT4X293M BECN1_HUMAN Gene/Protein Processing [11]
Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN OT81JS6K WRN_HUMAN Drug Response [12]
Caspase-2 (CASP2) OTUDYSPP CASP2_HUMAN Gene/Protein Processing [13]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Gene/Protein Processing [14]
DNA repair protein RAD51 homolog 1 (RAD51) OTNVWGC1 RAD51_HUMAN Drug Response [15]
DNA topoisomerase 1 (TOP1) OT51O0CF TOP1_HUMAN Drug Response [5]
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 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
6 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.
7 Phase I pharmacokinetic study of the novel antitumor agent SR233377. Clin Cancer Res. 2000 Aug;6(8):3088-94.
8 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.
9 Acridine derivatives activate p53 and induce tumor cell death through Bax. Cancer Biol Ther. 2005 Aug;4(8):893-8. doi: 10.4161/cbt.4.8.2134.
10 [Studies on programmed cell death induced by amsacrine and expression of bcl-2 in leukemia cell lines]. Zhonghua Zhong Liu Za Zhi. 1997 Sep;19(5):346-9.
11 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.
12 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.
13 Topoisomerase I and II inhibitors control caspase-2 pre-messenger RNA splicing in human cells. Mol Cancer Res. 2004 Jan;2(1):53-61.
14 High-throughput measurement of the Tp53 response to anticancer drugs and random compounds using a stably integrated Tp53-responsive luciferase reporter. Carcinogenesis. 2002 Jun;23(6):949-57. doi: 10.1093/carcin/23.6.949.
15 A novel interaction [corrected] of nucleolin with Rad51. Biochem Biophys Res Commun. 2006 May 26;344(1):206-13. doi: 10.1016/j.bbrc.2006.03.113. Epub 2006 Mar 29.