Details of the Drug

General Information of Drug (ID: DMU8L7C)

Drug Name
Mepacrine
Synonyms
quinacrine; mepacrine; atabrine; Acrinamine; Acriquine; 83-89-6; Quinactine; Antimalarina; Haffkinine; Akrichin; Italchine; acrichine; Erion; Mepacrinum; Quinacrine hydrochloride; Mepacrine [INN:BAN]; St 439; Mepacrinum [INN-Latin]; Mepacrina [INN-Spanish]; atebrin; Malaricida; Methoquine; Palacrin; Italchin; Pentilen; Palusan; Atebrine; Metochin; Mecryl; Quinacrine, Mepacrine; 3-Chloro-7-methoxy-9-(1-methyl-4-diethylaminobutylamino)acridine; 2-Methoxy-6-chloro-9-diethylaminopentylaminoacridine; HSDB 3253
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 400
Logarithm of the Partition Coefficient (xlogp) 6
Rotatable Bond Count (rotbonds) 9
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 4
ADMET Property
Absorption
The drug is rapidly absorbed from the gastrointestinal tract []
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 5.1 mL/min/kg [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 5 - 14 days [3]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 12.501 micromolar/kg/day [4]
Unbound Fraction
The unbound fraction of drug in plasma is 0.13% [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 45 L/kg [3]
Water Solubility
The ability of drug to dissolve in water is measured as 28.57 mg/mL [2]
Chemical Identifiers
Formula
C23H30ClN3O
IUPAC Name
4-N-(6-chloro-2-methoxyacridin-9-yl)-1-N,1-N-diethylpentane-1,4-diamine
Canonical SMILES
CCN(CC)CCCC(C)NC1=C2C=C(C=CC2=NC3=C1C=CC(=C3)Cl)OC
InChI
InChI=1S/C23H30ClN3O/c1-5-27(6-2)13-7-8-16(3)25-23-19-11-9-17(24)14-22(19)26-21-12-10-18(28-4)15-20(21)23/h9-12,14-16H,5-8,13H2,1-4H3,(H,25,26)
InChIKey
GPKJTRJOBQGKQK-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
237
ChEBI ID
CHEBI:8711
CAS Number
83-89-6
DrugBank ID
DB01103
TTD ID
D0O2DQ
VARIDT ID
DR01478
INTEDE ID
DR1377
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
Phospholipase A2 (PLA2G1B) TT9V5JH PA21B_HUMAN Inhibitor [1]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [6]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [6]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) OTSBQR6D PLCG1_HUMAN Post-Translational Modifications [7]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Gene/Protein Processing [8]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Regulation of Drug Effects [6]
Casein kinase I isoform alpha (CSNK1A1) OTJ6O1IC KC1A_HUMAN Gene/Protein Processing [9]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Gene/Protein Processing [9]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Protein Interaction/Cellular Processes [8]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Gene/Protein Processing [9]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Gene/Protein Processing [10]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Gene/Protein Processing [11]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Regulation of Drug Effects [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Discovery agent
ICD Disease Classification N.A.
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Phospholipase A2 (PLA2G1B) DTT PLA2G1B 2.65E-01 -0.08 -0.21
Breast cancer resistance protein (ABCG2) DTP BCRP 4.63E-01 -1.31E-01 -2.30E-01
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 1.34E-01 -2.79E-01 -7.05E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 9.81E-01 2.72E-01 6.95E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Involvement of protein kinase C activation in L-leucine-induced stimulation of protein synthesis in l6 myotubes. Cytotechnology. 2003 Nov;43(1-3):97-103.
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 Arginine-482 is not essential for transport of antibiotics, primary bile acids and unconjugated sterols by the human breast cancer resistance protein (ABCG2). Biochem J. 2005 Jan 15;385(Pt 2):419-26.
6 Quinacrine is mainly metabolized to mono-desethyl quinacrine by CYP3A4/5 and its brain accumulation is limited by P-glycoprotein. Drug Metab Dispos. 2006 Jul;34(7):1136-44.
7 Quinacrine is active in preclinical models of glioblastoma through suppressing angiogenesis, inducing oxidative stress and activating AMPK. Toxicol In Vitro. 2022 Sep;83:105420. doi: 10.1016/j.tiv.2022.105420. Epub 2022 Jun 17.
8 Quinacrine induces the apoptosis of human leukemia U937 cells through FOXP3/miR-183/-TrCP/SP1 axis-mediated BAX upregulation. Toxicol Appl Pharmacol. 2017 Nov 1;334:35-46. doi: 10.1016/j.taap.2017.08.019. Epub 2017 Sep 1.
9 Nanoquinacrine caused apoptosis in oral cancer stem cells by disrupting the interaction between GLI1 and catenin through activation of GSK3. Toxicol Appl Pharmacol. 2017 Sep 1;330:53-64. doi: 10.1016/j.taap.2017.07.008. Epub 2017 Jul 15.
10 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.
11 Multiple-endpoint in vitro carcinogenicity test in human cell line TK6 distinguishes carcinogens from non-carcinogens and highlights mechanisms of action. Arch Toxicol. 2021 Jan;95(1):321-336. doi: 10.1007/s00204-020-02902-3. Epub 2020 Sep 10.