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]
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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)

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

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]
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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
UNII: 00DPD30SOY
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]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6)_{Main DME}	DECB0K3	CP2D6_HUMAN	Substrate	[7]

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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]

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Molecular Interaction Atlas (MIA)

MIA Detail

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.