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]
------------------------------------------------------------------------------------

Affected Organisms

Humans and other mammals

ATC Code

A04AA03: Tropisetron

A04AA: Serotonin (5HT3) antagonists

A04A: ANTIEMETICS AND ANTINAUSEANTS

A04: ANTIEMETICS AND ANTINAUSEANTS

A: ALIMENTARY TRACT AND METABOLISM

A04AA03: Tropisetron

A04AA: Serotonin (5HT3) antagonists

A04A: ANTIEMETICS AND ANTINAUSEANTS

A04: ANTIEMETICS AND ANTINAUSEANTS

A: ALIMENTARY TRACT AND METABOLISM

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
UNII: 6I819NIK1W
DrugBank ID: DB11699
TTD ID: D0K0KH
INTEDE ID: DR1653

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
5-HT 3A receptor (HTR3A)	TTPC4TU	5HT3A_HUMAN	Antagonist	[6]

------------------------------------------------------------------------------------

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]

------------------------------------------------------------------------------------

Drug Off-Target (DOT)

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

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

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

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: 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.