Fexinidazole

Identification

Summary

Fexinidazole is an orally bioavailable 2-substituted 5-nitroimidazole used to treat early- and late-stage human African trypanosomiasis caused by Trypanosoma brucei gambiense.

Generic Name
Fexinidazole
DrugBank Accession Number
DB12265
Background

Human African trypanosomiasis (HAT, also colloquially referred to as sleeping sickness), caused by T. brucei gambiense and T. brucei rhodesiense, remains a moderate risk (>1/10,000 inhabitants per year in endemic areas) despite focussed control efforts. Transmitted by the bite of an infected tsetse fly, HAT is biphasic with a first (hemolymphatic) stage that progresses to a second (meningoencephalitic) stage in which patients experience progressively worsening neurological symptoms and eventually die if left untreated.1 Historical treatment options for meningoencephalitic HAT include melarsoprol, eflornithine, and nifurtimox/eflornithine combination therapy (NECT), though melarsoprol is highly toxic and each treatment requires lengthy infusions that are difficult to administer in resource-limited settings.1,3 Fexinidazole, which was originally developed in the 1970s/80s by Hoechst AG and subsequently rediscovered through the Drugs for Neglected Diseases Initiative (DNDi) in 2005, is the first all-oral treatment for first and second stage HAT caused by T. brucei gambiense.2,3

Fexinidazole received a positive opinion from the European Medicines Agency (EMA) in November 2018 and was approved by the FDA on July 16, 2021.2,7 It is currently marketed by Sanofi-Aventis.7

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 279.31
Monoisotopic: 279.067762465
Chemical Formula
C12H13N3O3S
Synonyms
  • Fexinidazole

Pharmacology

Indication

Fexinidazole is a nitroimidazole indicated for the treatment of both first-stage (hemolymphatic) and second-stage (meningoencephalitic) Trypanosoma brucei gambiense human African trypanosomiasis (HAT) in patients 6 years of age and older weighing at least 20 kg.7

Due to the decreased efficacy observed in patients with severe second stage HAT (cerebrospinal fluid white blood cell count (CSF-WBC) >100 cells/μL), fexinidazole should only be used in these patients if there are no other available treatment options.7

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Fexinidazole is a 2-substituted 5-nitroimidazole that is likely activated by parasitic nitroreductases to highly reactive species, leading to DNA and protein damage and eventual parasite death.2,3,7 The dosing schedule is designed to ensure a high enough concentration of fexinidazole and its reactive metabolites for at least 48 hours, which from in vitro studies was shown to be the minimum exposure time that was effectively trypanocidal.4,5 Although fexinidazole is effective in late-stage T. brucei gambiense HAT, it is less effective than NECT therapy in patients with severe (cerebrospinal fluid white blood cell count (CSF-WBC) >100 cells/μL at baseline) disease. It should only be used in these patients if there are no other available treatment options. Fexinidazole has been shown to prolong the QT interval in a dose-dependent manner and was also associated with a higher incidence of insomnia, headache, tremors, psychiatric disorders, and suicidal ideation in clinical trials; patients with pre-existing conditions or concomitant medications that could aggravate any of these effects should be treated with caution. In addition, fexinidazole has been associated with neutropenia and elevations in liver transaminases, which should be monitored. Nitroimidazoles like fexinidazole have been associated with a disulfiram-like reaction when used concomitantly with alcohol and psychotic reactions when taken with disulfiram itself; patients should avoid alcohol and disulfiram when taking fexinidazole.7

Mechanism of action

Human African trypanosomiasis (HAT) is caused by two subspecies of Trypanosoma brucei, T. brucei gambiense and T. brucei rhodesiense, with T. brucei gambiense HAT accounting for ~97% of the total disease burden. Transmitted by the bite of an infected tsetse fly, HAT begins as a local infection at the bite site before disseminating throughout the blood and reticuloendothelial system (first or hemolymphatic stage) and eventually crossing the blood-brain barrier (second or meningoencephalitic stage). First stage T. brucei gambiense HAT is characterized by fever, headache, swollen lymph nodes, pruritus, and other non-specific symptoms. Progression to the second stage results in progressive deterioration of neurological function, including sleep disturbances (HAT is also referred to as sleeping sickness), tremors, ataxia, abnormal behaviour, confusion, and coma; myocarditis and endocrine hypothalamic-hypophyseal dysfunction may also be present. If left untreated, HAT is fatal.1

Fexinidazole is the first all-oral treatment for T. brucei gambiense HAT.2 Both fexinidazole and its two main metabolites, a sulfoxide (M1) and sulfone (M2) metabolite, possess in vitro activity against T. brucei gambiense, T. brucei rhodesiense, and T. brucei brucei in the 0.2-0.9 μg/mL range.3,4 Further studies revealed in vivo efficacy in HAT animal models and acceptable toxicity profiles, both in animal and human subjects.3,4,5 Crucially, fexinidazole was shown to be non-inferior to existing nifurtimox/eflornithine combination therapy (NECT) in late-stage T. brucei gambiense infection.6

The precise mechanism of action of fexinidazole remains unknown. However, it is suggested that bacterial-like nitroreductases encoded by trypanosomes activate fexinidazole and its M1/M2 metabolites through reduction to form reactive intermediates capable of damaging DNA and proteins.2,3,7 Whole-body autoradiography of [14C]-labelled fexinidazole in rats revealed broad distribution into all tissues, including an observed brain-to-blood concentration ratio of 0.4-0.6.3 Therefore, fexinidazole is capable of direct toxicity against trypanosomes throughout the body and in the brain, which is consistent with its efficacy against both early and late-stage infections.3,4,6

Absorption

Fexinidazole is well absorbed, although the rate and extent of absorption are less than dose-proportional; after a 14-day administration schedule, the mean Cmax and AUClast increased by 1.17 and 1.34, or by 1.5 and 1.61, when the dose was either doubled or tripled.5 Following absorption, fexinidazole is rapidly converted to its M1 metabolite, which undergoes a slower transformation to M2 over time. This is reflected in the Tmax of fexinidazole, M1, and M2 as 4 (0-9), 4 (0-6), and 6 (0-24) hours, respectively.5,7

In healthy adults given an 1800 mg loading dose followed by 1200 mg daily over 14 days, the mean Cmax for fexinidazole was 1.6 ± 0.4 μg/mL on day 1, 0.8 ± 0.3 μg/mL on day 2, and 0.5 ± 0.2 μg/mL on day 3. The relevant values for M1 were 8.1 ± 2.2, 8.0 ± 2.3, and 5.9 ± 2.1, while for M2 they were 7.5 ± 3.3, 19.6 ± 5.4, and 12.5 ± 3.5 μg/mL. Similarly, the AUC for fexinidazole was 14.3 ± 2.6, 11.6 ± 2.2, and 7.0 ± 2.5, for M1 was 102.3 ± 28.5, 127.9 ± 49.2, and 84.2 ± 36.3, and for M2 was 110.1 ± 41.1, 391.5 ± 126.7, and 252.4 ± 73.6 μg*h/mL.5,7 Concomitant food intake increases the Cmax and AUC of fexinidazole, M1, and M2 by 2-5 fold without significantly changing the metabolite ratios.5,7

There are no clear effects of age, renal, or hepatic impairment on absorption or plasma parameters of fexinidazole or its metabolites; further studies may be required to confirm/refute these observations.7

Volume of distribution

Fexinidazole has an apparent volume of distribution of 3222 ± 1199 L.7

Protein binding

Fexinidazole, M1, and M2 are approximately 98, 41, and 57 percent bound to plasma proteins, respectively.5,7

Metabolism

Fexinidazole is metabolized by a variety of enzymes including the CYP450 enzymes CYP1A2, 2B6, 2C19, 2D6, 3A4, and 3A5 as well as flavin mono-oxygenase-3 (FMO-3). Fexinidazole is first transformed to the sulfoxide M1 and then the sulfone M2, which does not appear to undergo further metabolism.3,5,7

Hover over products below to view reaction partners

Route of elimination

Elimination is almost entirely extra-renal; roughly 0.75-3.15% of a fexinidazole dose was recovered in urine over 168 h, primarily as M1 and M2 metabolites.5,7

Half-life

Fexinidazole, M1, and M2 have mean day 10 half-lives of 15 ± 6, 16 ± 6, and 23 ± 4 hours, respectively.5,7

Clearance

Fexinidazole has a mean apparent day 4 clearance of 161 ± 37 L/h.7

Adverse Effects
Adverseeffects
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Toxicity

Healthy male adult volunteers were administered single or multiple daily doses of up to 3600 mg for 14 days and experienced elevated liver transaminases, vomiting, and panic attacks. Pediatric HAT patients given higher than recommended doses experienced vomiting, increased potassium, and decreased calcium levels. There is no specific antidote to fexinidazole; symptomatic and supportive measures are recommended in case of overdose.7

Rats and beagles given up to 800 mg/kg/day of fexinidazole showed mild appetite and body weight alterations but no clear hepatotoxicity. Fexinidazole did not induce any effects on embryo-fetal and postnatal development when administered to pregnant rats. Although fexinidazole is mutagenic in a standard Ames test, it is not anticipated to be genotoxic in humans.3

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Fexinidazole can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Fexinidazole can be increased when combined with Abatacept.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Fexinidazole.
AbirateroneThe serum concentration of Fexinidazole can be increased when it is combined with Abiraterone.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Fexinidazole.
AcamprosateThe excretion of Acamprosate can be decreased when combined with Fexinidazole.
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Fexinidazole.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Fexinidazole.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Fexinidazole.
AcrivastineThe risk or severity of adverse effects can be increased when Acrivastine is combined with Fexinidazole.
Interactions
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Food Interactions
  • Take with food. Food assists in fexinidazole absorption.

Products

Products2
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
FexinidazoleTablet600 mg/1Oralsanofi-aventis U.S. LLC2021-07-16Not applicableUS flag

Categories

ATC Codes
P01CA03 — Fexinidazole
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as nitroimidazoles. These are compounds containing an imidazole ring which bears a nitro group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azoles
Sub Class
Imidazoles
Direct Parent
Nitroimidazoles
Alternative Parents
Thiophenol ethers / 1,2,5-trisubstituted imidazoles / Phenoxy compounds / Phenol ethers / Nitroaromatic compounds / Alkyl aryl ethers / Alkylarylthioethers / N-substituted imidazoles / Heteroaromatic compounds / Organic oxoazanium compounds
show 7 more
Substituents
1,2,5-trisubstituted-imidazole / Alkyl aryl ether / Alkylarylthioether / Allyl-type 1,3-dipolar organic compound / Aromatic heteromonocyclic compound / Aryl thioether / Azacycle / Benzenoid / C-nitro compound / Ether
show 23 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Trypanosoma brucei gambiense

Chemical Identifiers

UNII
306ERL82IR
CAS number
59729-37-2
InChI Key
MIWWSGDADVMLTG-UHFFFAOYSA-N
InChI
InChI=1S/C12H13N3O3S/c1-14-11(13-7-12(14)15(16)17)8-18-9-3-5-10(19-2)6-4-9/h3-7H,8H2,1-2H3
IUPAC Name
1-methyl-2-{[4-(methylsulfanyl)phenoxy]methyl}-5-nitro-1H-imidazole
SMILES
CSC1=CC=C(OCC2=NC=C(N2C)[N+]([O-])=O)C=C1

References

Synthesis Reference

Winkelmann E, Raether W, Gebert U, Sinharay A (1977) Chemotherapeutically active nitro compounds. 4. 5-nitroimidazoles (Part I-IV). Arzneimittelforschung 27-28.

General References
  1. Bottieau E, Clerinx J: Human African Trypanosomiasis: Progress and Stagnation. Infect Dis Clin North Am. 2019 Mar;33(1):61-77. doi: 10.1016/j.idc.2018.10.003. [Article]
  2. Deeks ED: Fexinidazole: First Global Approval. Drugs. 2019 Feb;79(2):215-220. doi: 10.1007/s40265-019-1051-6. [Article]
  3. Torreele E, Bourdin Trunz B, Tweats D, Kaiser M, Brun R, Mazue G, Bray MA, Pecoul B: Fexinidazole--a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness. PLoS Negl Trop Dis. 2010 Dec 21;4(12):e923. doi: 10.1371/journal.pntd.0000923. [Article]
  4. Kaiser M, Bray MA, Cal M, Bourdin Trunz B, Torreele E, Brun R: Antitrypanosomal activity of fexinidazole, a new oral nitroimidazole drug candidate for treatment of sleeping sickness. Antimicrob Agents Chemother. 2011 Dec;55(12):5602-8. doi: 10.1128/AAC.00246-11. Epub 2011 Sep 12. [Article]
  5. Tarral A, Blesson S, Mordt OV, Torreele E, Sassella D, Bray MA, Hovsepian L, Evene E, Gualano V, Felices M, Strub-Wourgaft N: Determination of an optimal dosing regimen for fexinidazole, a novel oral drug for the treatment of human African trypanosomiasis: first-in-human studies. Clin Pharmacokinet. 2014 Jun;53(6):565-80. doi: 10.1007/s40262-014-0136-3. [Article]
  6. Mesu VKBK, Kalonji WM, Bardonneau C, Mordt OV, Blesson S, Simon F, Delhomme S, Bernhard S, Kuziena W, Lubaki JF, Vuvu SL, Ngima PN, Mbembo HM, Ilunga M, Bonama AK, Heradi JA, Solomo JLL, Mandula G, Badibabi LK, Dama FR, Lukula PK, Tete DN, Lumbala C, Scherrer B, Strub-Wourgaft N, Tarral A: Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial. Lancet. 2018 Jan 13;391(10116):144-154. doi: 10.1016/S0140-6736(17)32758-7. Epub 2017 Nov 4. [Article]
  7. FDA Approved Drug Products: Fexinidazole tablets for oral use [Link]
  8. Sigma-Aldrich: Fexinidazole SDS [Link]
PubChem Compound
68792
PubChem Substance
347828537
ChemSpider
62032
RxNav
2564146
ChEMBL
CHEMBL1631694
ZINC
ZINC000000001448
Wikipedia
Fexinidazole

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentTrypanosoma Brucei Gambiense; Infection / Trypanosomiasis; Gambian1
2CompletedTreatmentChagas' Disease (Chronic) Nos1
2TerminatedTreatmentVisceral Leishmaniasis1
2Unknown StatusTreatmentChagas Disease / Trypanosomiasis, South American1
2, 3CompletedTreatmentHuman African Trypanosomiasis (HAT)2
2, 3CompletedTreatmentHuman African Trypanosomiasis (HAT) / Trypanosoma Brucei Gambiense; Infection1
2, 3RecruitingTreatmentTrypanosoma Brucei Rhodesiense; Infection1
1CompletedNot AvailableTrypanosoma Brucei Gambiense; Infection1
1CompletedBasic SciencePK in Healthy Volunteers1
1TerminatedTreatmentTrypanosoma Brucei Gambiense; Infection1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral600 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
boiling point (°C)501MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.0927 mg/mLALOGPS
logP2.28ALOGPS
logP2.38ChemAxon
logS-3.5ALOGPS
pKa (Strongest Basic)1.03ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area70.19 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity72.64 m3·mol-1ChemAxon
Polarizability28.53 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
Curator comments
Both fexinidazole and M1 have the potential to induce CYP1A2.
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Torreele E, Bourdin Trunz B, Tweats D, Kaiser M, Brun R, Mazue G, Bray MA, Pecoul B: Fexinidazole--a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness. PLoS Negl Trop Dis. 2010 Dec 21;4(12):e923. doi: 10.1371/journal.pntd.0000923. [Article]
  2. FDA Approved Drug Products: Fexinidazole tablets for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
Curator comments
Both fexinidazole and M1 have the potential to induce CYP2B6.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Torreele E, Bourdin Trunz B, Tweats D, Kaiser M, Brun R, Mazue G, Bray MA, Pecoul B: Fexinidazole--a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness. PLoS Negl Trop Dis. 2010 Dec 21;4(12):e923. doi: 10.1371/journal.pntd.0000923. [Article]
  2. FDA Approved Drug Products: Fexinidazole tablets for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Fexinidazole as well as M1 may inhibit CYP2C19.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Torreele E, Bourdin Trunz B, Tweats D, Kaiser M, Brun R, Mazue G, Bray MA, Pecoul B: Fexinidazole--a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness. PLoS Negl Trop Dis. 2010 Dec 21;4(12):e923. doi: 10.1371/journal.pntd.0000923. [Article]
  2. FDA Approved Drug Products: Fexinidazole tablets for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Torreele E, Bourdin Trunz B, Tweats D, Kaiser M, Brun R, Mazue G, Bray MA, Pecoul B: Fexinidazole--a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness. PLoS Negl Trop Dis. 2010 Dec 21;4(12):e923. doi: 10.1371/journal.pntd.0000923. [Article]
  2. FDA Approved Drug Products: Fexinidazole tablets for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Torreele E, Bourdin Trunz B, Tweats D, Kaiser M, Brun R, Mazue G, Bray MA, Pecoul B: Fexinidazole--a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness. PLoS Negl Trop Dis. 2010 Dec 21;4(12):e923. doi: 10.1371/journal.pntd.0000923. [Article]
  2. FDA Approved Drug Products: Fexinidazole tablets for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Trimethylamine monooxygenase activity
Specific Function
Involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. It N-oxygenates primary aliphatic alkylamines as well as secondary and tertiary amines. Plays an impor...
Gene Name
FMO3
Uniprot ID
P31513
Uniprot Name
Dimethylaniline monooxygenase [N-oxide-forming] 3
Molecular Weight
60032.975 Da
References
  1. Tarral A, Blesson S, Mordt OV, Torreele E, Sassella D, Bray MA, Hovsepian L, Evene E, Gualano V, Felices M, Strub-Wourgaft N: Determination of an optimal dosing regimen for fexinidazole, a novel oral drug for the treatment of human African trypanosomiasis: first-in-human studies. Clin Pharmacokinet. 2014 Jun;53(6):565-80. doi: 10.1007/s40262-014-0136-3. [Article]
  2. FDA Approved Drug Products: Fexinidazole tablets for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Torreele E, Bourdin Trunz B, Tweats D, Kaiser M, Brun R, Mazue G, Bray MA, Pecoul B: Fexinidazole--a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness. PLoS Negl Trop Dis. 2010 Dec 21;4(12):e923. doi: 10.1371/journal.pntd.0000923. [Article]
  2. FDA Approved Drug Products: Fexinidazole tablets for oral use [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. FDA Approved Drug Products: Fexinidazole tablets for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. FDA Approved Drug Products: Fexinidazole tablets for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
This transporter is inhibited by both fexinidazole and its M2 metabolite.
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. FDA Approved Drug Products: Fexinidazole tablets for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
This transporter is inhibited by both fexinidazole and its M2 metabolite.
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. FDA Approved Drug Products: Fexinidazole tablets for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
This transporter is inhibited by both fexinidazole and its M1 and M2 metabolites.
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. FDA Approved Drug Products: Fexinidazole tablets for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
This transporter is inhibited by both fexinidazole and its M1 and M2 metabolites.
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. FDA Approved Drug Products: Fexinidazole tablets for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
This transporter is inhibited by both fexinidazole and its M1 and M2 metabolites.
General Function
Drug transmembrane transporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
  1. FDA Approved Drug Products: Fexinidazole tablets for oral use [Link]

Drug created on October 20, 2016 21:45 / Updated on August 28, 2021 08:41