General Information of Drug (ID: DMOYE70)

Drug Name
Fexinidazole
Synonyms
Fexinidazole (human African trypanosomiasis); Fexinidazole (African sleeping sickness), Drugs for Neglected Diseases initiative; Fexinidazole (HAT), Drugs for Neglected Diseases initiative; Fexinidazole (human African trypanosomiasis), Drugs for Neglected Diseases initiative
Indication
Disease Entry ICD 11 Status REF
African trypanosomiasis 1F51 Approved [1]
Trypanosomiasis 1D51-1F53 Phase 2/3 [2]
Affected Organisms
Trypanosoma brucei gambiense
ATC Code
P01CA03: Fexinidazole
P01CA: Nitroimidazole derivatives
P01C: AGENTS AGAINST LEISHMANIASIS AND TRYPANOSOMIASIS
P01: ANTIPROTOZOALS
P: ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 279.32
Logarithm of the Partition Coefficient (xlogp) 2.5
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 5
ADMET Property
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 1.6 +/- 0.4 mg/L [3]
Clearance
The clearance of drug is 161 +/- 37 L/h [4]
Elimination
Elimination is almost entirely extra-renal, and roughly 0.75-3.15% of a drug dose was recovered in urine over 168 h [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 15 +/- 6 hours [3]
Metabolism
The drug is metabolized via a variety of enzymes including the CYP450 enzymes CYP1A2, 2B6, 2C19, 2D6, 3A4, and 3A5 as well as flavin mono-oxygenase-3 (FMO-3) [5]
Vd
The volume of distribution (Vd) of drug is 3222 +/- 1199 L [4]
Chemical Identifiers
Formula
C12H13N3O3S
IUPAC Name
1-methyl-2-[(4-methylsulfanylphenoxy)methyl]-5-nitroimidazole
Canonical SMILES
CN1C(=CN=C1COC2=CC=C(C=C2)SC)[N+](=O)[O-]
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
InChIKey
MIWWSGDADVMLTG-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
68792
CAS Number
59729-37-2
UNII
306ERL82IR
DrugBank ID
DB12265
TTD ID
D00RWW
INTEDE ID
DR1873
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [6]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [6]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Substrate [6]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [6]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [6]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Substrate [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 FDA Approved Drug Products from FDA Official Website. 2021. Application Number: 214429.
2 ClinicalTrials.gov (NCT02169557) Efficacy and Safety of Fexinidazole in Patients With Stage 1 or Early Stage 2 Human African Trypanosomiasis (HAT) Due to T.b. Gambiense: a Prospective, Multicentre, Open-label Cohort Study, plug-in to the Pivotal Study. U.S. National Institutes of Health.
3 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.
4 FDA Approved Drug Products: Fexinidazole tablets for oral use
5 Squirewell EJ, Qin X, Duffel MW: Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50. doi: 10.1124/dmd.114.059709. Epub 2014 Aug 25.
6 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.