Details of the Drug

General Information of Drug (ID: DMNSJ7V)

Drug Name

Tropisetron

Synonyms

Navoban; Novaban; TKT; ICS-205930; Navoban (TN); Tropisetron (INN); [(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 1H-indole-3-carboxylate; (3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl 1H-indole-3-carboxylate

Indication

Disease Entry	ICD 11	Status	REF
Fibromyalgia	MG30.01	Approved	[1]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

284.35

Logarithm of the Partition Coefficient (xlogp)

3.8

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
Bioavailability: 66% of drug becomes completely available to its intended biological destination(s) [3]
Clearance: The clearance of drug is 1800 mL/min []
Elimination: 8% 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 5.7 hours [4]
Metabolism: The drug is metabolized via the hydroxylation at the 5, 6 or 7 positions of its indole ring, followed by a conjugation reaction to the glucuronide or sulphate []
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.2512 micromolar/kg/day [5]
Vd: The volume of distribution (Vd) of drug is 400-600 L []
Water Solubility: The ability of drug to dissolve in water is measured as 11 mg/mL [2]

Chemical Identifiers

Formula: C17H20N2O2
IUPAC Name: [(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 1H-indole-3-carboxylate
Canonical SMILES: CN1[C@@H]2CC[C@H]1CC(C2)OC(=O)C3=CNC4=CC=CC=C43
InChI: InChI=1S/C17H20N2O2/c1-19-11-6-7-12(19)9-13(8-11)21-17(20)15-10-18-16-5-3-2-4-14(15)16/h2-5,10-13,18H,6-9H2,1H3/t11-,12+,13?
InChIKey: ZNRGQMMCGHDTEI-FUNVUKJBSA-N

Cross-matching ID

PubChem CID: 656665
ChEBI ID: CHEBI:32269
CAS Number: 89565-68-4
DrugBank ID: DB11699
TTD ID: D0K0KH
INTEDE ID: DR1653

Combinatorial Drugs (CBD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 3A receptor (HTR3A)	TTPC4TU	5HT3A_HUMAN	Antagonist	[6]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[7]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[8]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[9]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[10]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Fibromyalgia

ICD Disease Classification

MG30.01

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
5-HT 3A receptor (HTR3A)	DTT	HTR3A	6.60E-01	1.08E-02	0.04
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	8.20E-01	-1.63E-03	-1.13E-02
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	7.48E-04	3.43E-01	6.77E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	9.40E-01	-2.17E-02	-4.03E-02

Molecular Expression Atlas (MEA)

MEA Detail

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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: 260).
2	BDDCS applied to over 900 drugs
3	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	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
6	Emerging therapies for fibromyalgia. Expert Opin Emerg Drugs. 2008 Mar;13(1):53-62.
7	Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of dolasetron. Comparison with other indole-containing 5-HT3 antagonists. Drug Metab Dispos. 1996 May;24(5):602-9.
8	Cytochrome P450 2D6 metabolism and 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. Med Sci Monit. 2005 Oct;11(10):RA322-8.
9	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
10	Serotonin type-3 receptor antagonists selectively kill melanoma cells through classical apoptosis, microtubule depolymerisation, ERK activation, and NF-B downregulation. Cell Biol Toxicol. 2023 Jun;39(3):1119-1135. doi: 10.1007/s10565-021-09667-0. Epub 2021 Oct 15.