FEXINIDAZOLE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H13N3O3S
Molecular Weight	279.315
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CSC1=CC=C(OCC2=NC=C(N2C)[N+]([O-])=O)C=C1

InChI

InChIKey=MIWWSGDADVMLTG-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Molecular Formula	C12H13N3O3S
Molecular Weight	279.315
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

Fexinidazole is an antiparasitic drug, which is in the phase III of clinical trial for the treatment of Human African Trypanosomiasis, and in the phase II for the treatment Disease, Chagas and Visceral Leishmaniosis. However, for the Visceral Leishmaniosis, studies were terminated, due to lack of efficacy. Fexinidazole rapidly metabolized to two active metabolites, a sulfone and a sulfoxide, which prolong the pharmacological action of parent drug. These metabolites retaine trypanocidal activity but are less effective in nifurtimox-resistant lines, which can lead to the potential danger in the use of fexinidazole as a monotherapy.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
bacterial DNA synthesis 1	Inhibitor 8,504

Conditions

Condition	Modality	Highest Phase	Product
African trypanosomiasis 11	Curative	Phase III 665	Unknown
visceral leishmaniasis 1	Curative	Phase II 1,147	Unknown
Chagas disease 19	Curative	Phase II 1,147	Unknown

C_max

Value	Dose	Analyte	Population
130 ng/mL	100 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
139 ng/mL	200 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
171 ng/mL	400 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
532 ng/mL	800 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
479 ng/mL	1200 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
483 ng/mL	1800 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
749 ng/mL	3000 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
1790 ng/mL	1200 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
303 ng/mL	1200 mg 1 times / day multiple, oral	FEXINIDAZOLE plasma	Homo sapiens
516 ng/mL	2400 mg 1 times / day multiple, oral	FEXINIDAZOLE plasma	Homo sapiens
653 ng/mL	3600 mg 1 times / day multiple, oral	FEXINIDAZOLE plasma	Homo sapiens
636.05 ng/mL	3600 mg 1 times / day multiple, oral	FEXINIDAZOLE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
1287 ng × h/mL	100 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
1384 ng × h/mL	200 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
2075 ng × h/mL	400 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
7387 ng × h/mL	800 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
5492 ng × h/mL	1200 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
6094 ng × h/mL	1800 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
12627 ng × h/mL	3000 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
21636 ng × h/mL	1200 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
3718 ng × h/mL	1200 mg 1 times / day multiple, oral	FEXINIDAZOLE plasma	Homo sapiens
7085 ng × h/mL	2400 mg 1 times / day multiple, oral	FEXINIDAZOLE plasma	Homo sapiens
9625 ng × h/mL	3600 mg 1 times / day multiple, oral	FEXINIDAZOLE plasma	Homo sapiens
9300.62 ng × h/mL	3600 mg 1 times / day multiple, oral	FEXINIDAZOLE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
9 h	100 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
12 h	200 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
15 h	400 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
13 h	800 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
9 h	1200 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
10 h	1800 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
13 h	3000 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
11 h	1200 mg single, oral	FEXINIDAZOLE plasma	Homo sapiens
10 h	3600 mg 1 times / day multiple, oral	FEXINIDAZOLE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
8.45%	3600 mg 1 times / day multiple, oral		FEXINIDAZOLE plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
3600 mg 1 times / day multiple, oral Highest studied dose	healthy, ADULT	Disc. AE: AST increased, ALT increased...
3600 mg single, oral Highest studied dose	healthy, ADULT
2400 mg 1 times / day multiple, oral Studied dose	healthy, ADULT	Disc. AE: Headache, Anxiety...

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AEs

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AE	Significance	Dose	Population
ALT increased	16.7% Disc. AE	3600 mg 1 times / day multiple, oral Highest studied dose	healthy, ADULT
AST increased	16.7% Disc. AE	3600 mg 1 times / day multiple, oral Highest studied dose	healthy, ADULT
Anxiety	16.7% Disc. AE	2400 mg 1 times / day multiple, oral Studied dose	healthy, ADULT
Diarrhea	16.7% Disc. AE	2400 mg 1 times / day multiple, oral Studied dose	healthy, ADULT
Headache	16.7% Disc. AE	2400 mg 1 times / day multiple, oral Studied dose	healthy, ADULT

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,946 inhibitor 2,252 supressor 22	inhibitor 2,438 substrate 1,193	inhibitor 2,507 substrate 1,388	inhibitor 2,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A5 136 OAT3 747 MATE2-K 77 OCT2 779 CYP2C19 2,057 MATE1 415 OAT1 725 CYP1A2 2,153 CYP2B6 926 OATP1B1 1,079 CYP2C8 1,057 BCRP 910 OATP1B3 961 P-gp 1,741 OCT1 620	FMO1 25 CYP2B6 776 CYP2C8 810 CYP1A2 1,197 P-gp 2,052 FMO5 5 CYP4F2 11 CYP2J2 71 FMO3 77 CYP1A1 389 CYP2A6 626 CYP2C19 1,119 CYP3A5 446	CYP2B6 669 CYP1A2 832

Drug as perpetrator

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Target	Modality	Activity	Metabolite
P-gp 1,932	inhibitor 4,027	no [IC50 >100 uM]
OAT1 730	inhibitor 4,027	no [IC50 >251 uM]	Fexinidazole sulfoxide 1
OCT2 782	inhibitor 4,027	no [IC50 >251 uM]	Fexinidazole sulfoxide 1
P-gp 1,932	inhibitor 4,027	no [IC50 >300 uM]	Fexinidazole sulfone 1
CYP3A4 2,633	inhibitor 4,027	no [IC50 >302 uM]	Fexinidazole sulfone 1

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Drug as victim

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Target	Modality	Activity
CYP2B6 776	substrate 4,014	no
CYP2C8 810	substrate 4,014	weak
CYP2C9 1,193	substrate 4,014	weak
CYP2D6 1,388	substrate 4,014	weak
P-gp 2,052	substrate 4,014	weak

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2,263	inhibitor 2,237		Fexinidazole sulfone 1

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PubMed

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Title	Date	PubMed
The anti-tubercular drug delamanid as a potential oral treatment for visceral leishmaniasis.	2016 May 24	27215734

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Patents

Sample Use Guides

In Vivo Use Guide

Fexinidazole, 600 mg tablets given by oral route, after the main daily meal (within 30 minutes from the start of the meal), at the daily dose of: 1 800 mg (3 tablets) once a day for 4 days, followed by 1 200 mg (2 tablets) once a day for 6 days. Total duration of treatment will be 10 days.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical
Record UNII	306ERL82IR
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

HOE-239

Preferred Name

English

FEXINIDAZOLE

Official Name

English

1-METHYL-2-((P-(METHYLTHIO)PHENOXY)METHYL)-5-NITROIMIDAZOLE

Common Name

English

fexinidazole [INN]

Common Name

English

1-Methyl-2-{[4-(methylthio)phenoxy]methyl}-5-nitro-1H-imidazole

Systematic Name

English

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Classification Tree

Code System

Code

Antiparasitic Agent

NCI_THESAURUS

C277

Nitroimidazole derivatives

WHO-ATC

P01CA03

Designated/Approved

FDA ORPHAN DRUG

513915

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Code System

Code

Type

Description

NCI_THESAURUS

C65680

PRIMARY

PUBCHEM

68792

PRIMARY

EVMPD

SUB07618MIG

PRIMARY

CAS

59729-37-2

PRIMARY

WIKIPEDIA

FEXINIDAZOLE

PRIMARY

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Related Record

Type

Details


					306ERL82IR

FEXINIDAZOLE

ACTIVE MOIETY

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SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator