Details of the Drug

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]
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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)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

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
DrugBank ID: DB12265
TTD ID: D00RWW
INTEDE ID: DR1873

Repurposed Drugs (RPD)

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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]

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Molecular Interaction Atlas (MIA)

MIA Detail

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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.