Details of the Drug

General Information of Drug (ID: DMCP2TS)

Drug Name
Nomifensine
Synonyms
Linamiphen; Nomifenison; Nomifensin; Nomifensina; Nomifensinum; Nomiphensine; Nomifensina [INN-Spanish]; Nomifensine [INN:BAN]; Nomifensine maleate(USAN); Nomifensinum [INN-Latin]; D,L-nomifensine; Nomifensine Maleate (1:1); R/S-nomifensine; (+)-Nomifensine; (+)-Nomiphensine; (+-)-1,2,3,4-Tetrahydro-2-methyl-4-phenyl-8-isoquinolinamine; (+-)-Nomifensin; (+-)-Nomifensine; (R)-1,2,3,4-Tetrahydro-2-methyl-4-phenyl-8-isoquinolinamine; 2-Methyl-4-phenyl-1,2,3,4-tetrahydro-8-isoquinolinamine; 2-Methyl-4-phenyl-1,2,3,4-tetrahydro-8-isoquinolinamine 2-butenedioate; 2-Methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine; 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-8-amine; 2-methyl-4-phenyl-3,4-dihydro-1H-isoquinolin-8-amine; 8-Amino-1,2,3,4-tetrahydro-2-methyl-4-phenylisochinolin; 8-Amino-1,2,3,4-tetrahydro-2-methyl-4-phenylisoquinoline; 8-Amino-1,2,3,4-tetrahydro-2-methyl-4-phenylisoquinoline maleate (1:1); 8-Amino-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 8-Isoquinolinamine, 1,2,3,4-tetrahydro-2-methyl-4-phenyl; 8-Isoquinolinamine, 1,2,3,4-tetrahydro-2-methyl-4-phenyl-(9CI)
Indication
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Withdrawn from market [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 238.33
Logarithm of the Partition Coefficient (xlogp) 2.6
Rotatable Bond Count (rotbonds) 1
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 2
ADMET Property
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 22 mL/min/kg [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 6.5 hours [3]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 11.988 micromolar/kg/day [4]
Unbound Fraction
The unbound fraction of drug in plasma is 0.4% [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 6 L/kg [3]
Chemical Identifiers
Formula
C16H18N2
IUPAC Name
2-methyl-4-phenyl-3,4-dihydro-1H-isoquinolin-8-amine
Canonical SMILES
CN1CC(C2=C(C1)C(=CC=C2)N)C3=CC=CC=C3
InChI
InChI=1S/C16H18N2/c1-18-10-14(12-6-3-2-4-7-12)13-8-5-9-16(17)15(13)11-18/h2-9,14H,10-11,17H2,1H3
InChIKey
XXPANQJNYNUNES-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
4528
ChEBI ID
CHEBI:116225
CAS Number
24526-64-5
DrugBank ID
DB04821
TTD ID
D06BPG
VARIDT ID
DR00944

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Dopamine D2 receptor (D2R) TTEX248 DRD2_HUMAN Antagonist [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Dimethylaniline oxidase 5 (FMO5)
Main DME 		DEBMX7C FMO5_HUMAN Substrate [6]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Gene/Protein Processing [7]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Gene/Protein Processing [7]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Gene/Protein Processing [7]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Gene/Protein Processing [8]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Gene/Protein Processing [7]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Gene/Protein Processing [7]
Synaptic vesicular amine transporter (SLC18A2) OTUOMMM6 VMAT2_HUMAN Protein Interaction/Cellular Processes [9]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Breast cancer
ICD Disease Classification 2C60-2C65
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Dopamine D2 receptor (D2R) DTT DRD2 2.50E-02 -0.08 -0.49
Dimethylaniline oxidase 5 (FMO5) DME FMO5 6.17E-04 1.66E-01 5.17E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4792).
2 BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional 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 Pharmacologically induced, subsecond dopamine transients in the caudate-putamen of the anesthetized rat. Synapse. 2007 Jan;61(1):37-9.
6 Drug metabolism by flavin-containing monooxygenases of human and mouse. Expert Opin Drug Metab Toxicol. 2017 Feb;13(2):167-181.
7 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
8 Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
9 Synaptic vesicular monoamine transporter expression: distribution and pharmacologic profile. Brain Res Mol Brain Res. 1994 Mar;22(1-4):219-26. doi: 10.1016/0169-328x(94)90050-7.