Details of the Drug

General Information of Drug (ID: DMJ7YDS)

• Drug Name: Dexfenfluramine
• Synonyms: DEXFENFLURAN; Dexfenfluramine (INN); Redux (TN); (2S)-N-ethyl-1-[3-(trifluoromethyl)phenyl]propan-2-amine; (S)-N-ethyl-1-[3-(trifluoromethyl)phenyl]propan-2-amine

Indication

Disease Entry	ICD 11	Status	REF
Obesity	5B81	Withdrawn from market	[1]

• Therapeutic Class: Appetite Depressants
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 231.26
  Topological Polar Surface Area (xlogp); 3.4
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  Absorption: The drug is well-absorbed from the gastrointestinal tract [2]
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
  Bioavailability: 89% of drug becomes completely available to its intended biological destination(s) [4]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 11 mL/min/kg [5]
  Half-life: The concentration or amount of drug in body reduced by one-half in 17 - 20 hours [5]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 1.853 micromolar/kg/day [6]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.66% [5]
  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 11 L/kg [5]
• Chemical Identifiers:
  Formula: C12H16F3N
  IUPAC Name: (2S)-N-ethyl-1-[3-(trifluoromethyl)phenyl]propan-2-amine
  Canonical SMILES: CCN[C@@H](C)CC1=CC(=CC=C1)C(F)(F)F
  InChI: InChI=1S/C12H16F3N/c1-3-16-9(2)7-10-5-4-6-11(8-10)12(13,14)15/h4-6,8-9,16H,3,7H2,1-2H3/t9-/m0/s1
  InChIKey: DBGIVFWFUFKIQN-VIFPVBQESA-N
• Cross-matching ID:
  PubChem CID: 66265
  ChEBI ID: CHEBI:439329
  CAS Number: 3239-44-9
  DrugBank ID: DB01191
  TTD ID: D0F9SG
  INTEDE ID: DR0466

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Inhibitor	[7]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[8]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[9]

Molecular Expression Atlas of This Drug

• The Studied Disease: Obesity
• ICD Disease Classification: 5B81

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Serotonin transporter (SERT)	DTT	SLC6A4	8.76E-01	7.18E-05	6.19E-04
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	8.46E-01	-6.63E-03	-4.49E-02
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	8.70E-01	2.98E-02	1.22E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Dexfenfluramine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Methylene blue	DMJAPE7	Major	Additive serotonergic effects by the combination of Dexfenfluramine and Methylene blue.	Acquired methaemoglobinaemia [3A93]	[37]
Oliceridine	DM6MDCF	Moderate	Additive CNS depression effects by the combination of Dexfenfluramine and Oliceridine.	Acute pain [MG31]	[38]
Inotersen	DMJ93CT	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Inotersen.	Amyloidosis [5D00]	[39]
Dronedarone	DMA8FS5	Moderate	Decreased metabolism of Dexfenfluramine caused by Dronedarone mediated inhibition of CYP450 enzyme.	Angina pectoris [BA40]	[40]
Trastuzumab Emtansine	DMU1LXS	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Trastuzumab Emtansine.	Breast cancer [2C60-2C6Y]	[41]
Dihydrocodeine	DMB0FWL	Moderate	Additive serotonergic effects by the combination of Dexfenfluramine and Dihydrocodeine.	Chronic pain [MG30]	[38]
Levomilnacipran	DMV26S8	Major	Additive serotonergic effects by the combination of Dexfenfluramine and Levomilnacipran.	Chronic pain [MG30]	[42]
Regorafenib	DMHSY1I	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Regorafenib.	Colorectal cancer [2B91]	[39]
Ardeparin	DMYRX8B	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Ardeparin.	Coronary thrombosis [BA43]	[39]
Rivaroxaban	DMQMBZ1	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Rivaroxaban.	Deep vein thrombosis [BD71]	[39]
Vilazodone	DM4LECQ	Major	Additive serotonergic effects by the combination of Dexfenfluramine and Vilazodone.	Depression [6A70-6A7Z]	[42]
Vortioxetine	DM6F1PU	Major	Additive serotonergic effects by the combination of Dexfenfluramine and Vortioxetine.	Depression [6A70-6A7Z]	[42]
Isocarboxazid	DMAF1NB	Major	Additive serotonergic effects by the combination of Dexfenfluramine and Isocarboxazid.	Depression [6A70-6A7Z]	[43]
Milnacipran	DMBFE74	Major	Additive serotonergic effects by the combination of Dexfenfluramine and Milnacipran.	Depression [6A70-6A7Z]	[42]
Desvenlafaxine	DMHD4PE	Major	Additive serotonergic effects by the combination of Dexfenfluramine and Desvenlafaxine.	Depression [6A70-6A7Z]	[42]
Clomipramine	DMINRKW	Major	Additive serotonergic effects by the combination of Dexfenfluramine and Clomipramine.	Depression [6A70-6A7Z]	[42]
Tazemetostat	DMWP1BH	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Tazemetostat.	Follicular lymphoma [2A80]	[41]
Mirabegron	DMS1GYT	Moderate	Decreased metabolism of Dexfenfluramine caused by Mirabegron mediated inhibition of CYP450 enzyme.	Functional bladder disorder [GC50]	[44]
Avapritinib	DMK2GZX	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[41]
Cobicistat	DM6L4H2	Moderate	Decreased metabolism of Dexfenfluramine caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[45]
Givosiran	DM5PFIJ	Moderate	Decreased metabolism of Dexfenfluramine caused by Givosiran mediated inhibition of CYP450 enzyme.	Inborn porphyrin/heme metabolism error [5C58]	[46]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of lowers seizure threshold by the combination of Dexfenfluramine and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[47]
Dacomitinib	DMOH8VY	Moderate	Decreased metabolism of Dexfenfluramine caused by Dacomitinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[48]
Ibrutinib	DMHZCPO	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Ibrutinib.	Mature B-cell lymphoma [2A85]	[39]
Ponatinib	DMYGJQO	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Ponatinib.	Mature B-cell lymphoma [2A85]	[39]
Vemurafenib	DM62UG5	Moderate	Decreased metabolism of Dexfenfluramine caused by Vemurafenib mediated inhibition of CYP450 enzyme.	Melanoma [2C30]	[49]
Exjade	DMHPRWG	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Exjade.	Mineral absorption/transport disorder [5C64]	[39]
Panobinostat	DM58WKG	Major	Increased risk of bleeding by the combination of Dexfenfluramine and Panobinostat.	Multiple myeloma [2A83]	[39]
Ozanimod	DMT6AM2	Moderate	Additive serotonergic effects by the combination of Dexfenfluramine and Ozanimod.	Multiple sclerosis [8A40]	[43]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Dexfenfluramine caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[50]
Nilotinib	DM7HXWT	Moderate	Decreased metabolism of Dexfenfluramine caused by Nilotinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[51]
Ruxolitinib	DM7Q98D	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Ruxolitinib.	Myeloproliferative neoplasm [2A20]	[39]
Dasatinib	DMJV2EK	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Dasatinib.	Myeloproliferative neoplasm [2A20]	[39]
Prasugrel	DM7MT6E	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Prasugrel.	Myocardial infarction [BA41-BA43]	[39]
Vorapaxar	DMA16BR	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Vorapaxar.	Myocardial infarction [BA41-BA43]	[39]
Rolapitant	DM8XP26	Moderate	Decreased metabolism of Dexfenfluramine caused by Rolapitant mediated inhibition of CYP450 enzyme.	Nausea/vomiting [MD90]	[52]
Oxymorphone	DM65AGJ	Moderate	Additive CNS depression effects by the combination of Dexfenfluramine and Oxymorphone.	Pain [MG30-MG3Z]	[38]
Safinamide	DM0YWJC	Major	Additive serotonergic effects by the combination of Dexfenfluramine and Safinamide.	Parkinsonism [8A00]	[43]
Rasagiline	DM3WKQ4	Major	Additive serotonergic effects by the combination of Dexfenfluramine and Rasagiline.	Parkinsonism [8A00]	[43]
Choline salicylate	DM8P137	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[41]
ABIRATERONE	DM8V75C	Moderate	Decreased metabolism of Dexfenfluramine caused by ABIRATERONE mediated inhibition of CYP450 enzyme.	Prostate cancer [2C82]	[53]
Epoprostenol	DMUTYR2	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Epoprostenol.	Pulmonary hypertension [BB01]	[39]
Aripiprazole	DM3NUMH	Moderate	Decreased metabolism of Dexfenfluramine caused by Aripiprazole mediated inhibition of CYP450 enzyme.	Schizophrenia [6A20]	[54]
Pitolisant	DM8RFNJ	Moderate	Decreased metabolism of Dexfenfluramine caused by Pitolisant mediated inhibition of CYP450 enzyme.	Somnolence [MG42]	[50]
Caplacizumab	DMPUKA7	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Caplacizumab.	Thrombocytopenia [3B64]	[39]
Apixaban	DM89JLN	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Apixaban.	Thrombosis [DB61-GB90]	[39]
Cangrelor	DM8JRH0	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Cangrelor.	Thrombosis [DB61-GB90]	[41]
Brilinta	DMBR01X	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Brilinta.	Thrombosis [DB61-GB90]	[39]
Cabozantinib	DMIYDT4	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Cabozantinib.	Thyroid cancer [2D10]	[39]
Betrixaban	DM2C4RF	Moderate	Increased risk of bleeding by the combination of Dexfenfluramine and Betrixaban.	Venous thromboembolism [BD72]	[41]

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