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

Structure Search

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

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25039421 | https://www.ncbi.nlm.nih.gov/pubmed/20439607 | https://www.ncbi.nlm.nih.gov/pubmed/24841257

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 Target ID: bacterial DNA synthesis Sources: https://www.ncbi.nlm.nih.gov/pubmed/20439607	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
African trypanosomiasis 11 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25039421	Curative	Phase III 665	Unknown Approved Use Unknown
visceral leishmaniasis 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22301556	Curative	Phase II 1147	Unknown Approved Use Unknown
Chagas disease 19 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24841257	Curative	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
130 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
139 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
171 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
532 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
479 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
483 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	1800 mg single, oral dose: 1800 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
749 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	3000 mg single, oral dose: 3000 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1790 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT
303 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	1200 mg 1 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
516 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	2400 mg 1 times / day multiple, oral dose: 2400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
653 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	3600 mg 1 times / day multiple, oral dose: 3600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
636.05 ng/mL OTHER GOV'T https://www.ema.europa.eu/en/documents/outside-eu-assessment-report/fexinidazole-winthrop-assessment-report_en.pdf	3600 mg 1 times / day multiple, oral dose: 3600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
1287 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1384 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2075 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7387 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5492 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6094 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	1800 mg single, oral dose: 1800 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
12627 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	3000 mg single, oral dose: 3000 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
21636 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT
3718 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	1200 mg 1 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7085 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	2400 mg 1 times / day multiple, oral dose: 2400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
9625 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	3600 mg 1 times / day multiple, oral dose: 3600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
9300.62 ng × h/mL OTHER GOV'T https://www.ema.europa.eu/en/documents/outside-eu-assessment-report/fexinidazole-winthrop-assessment-report_en.pdf	3600 mg 1 times / day multiple, oral dose: 3600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
12 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
15 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
13 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
10 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	1800 mg single, oral dose: 1800 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
13 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	3000 mg single, oral dose: 3000 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
11 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24535888/	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT
10 h OTHER GOV'T https://www.ema.europa.eu/en/documents/outside-eu-assessment-report/fexinidazole-winthrop-assessment-report_en.pdf	3600 mg 1 times / day multiple, oral dose: 3600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
8.45% OTHER GOV'T https://www.ema.europa.eu/en/documents/outside-eu-assessment-report/fexinidazole-winthrop-assessment-report_en.pdf	3600 mg 1 times / day multiple, oral dose: 3600 mg route of administration: Oral experiment type: MULTIPLE co-administered:		FEXINIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
3600 mg 1 times / day multiple, oral Highest studied dose Dose: 3600 mg, 1 times / day Route: oral Route: multiple Dose: 3600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/	Disc. AE: AST increased, ALT increased... AEs leading to discontinuation/dose reduction: AST increased (16.7%) ALT increased (16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/
3600 mg single, oral Highest studied dose Dose: 3600 mg Route: oral Route: single Dose: 3600 mg Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/	Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/
2400 mg 1 times / day multiple, oral Studied dose Dose: 2400 mg, 1 times / day Route: oral Route: multiple Dose: 2400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/	Disc. AE: Headache, Anxiety... AEs leading to discontinuation/dose reduction: Headache (16.7%) Anxiety (16.7%) Vomiting (16.7%) Diarrhea (16.7%) Myalgia (16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/

AEs

AE	Significance	Dose	Population
ALT increased	16.7% Disc. AE	3600 mg 1 times / day multiple, oral Highest studied dose Dose: 3600 mg, 1 times / day Route: oral Route: multiple Dose: 3600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/
AST increased	16.7% Disc. AE	3600 mg 1 times / day multiple, oral Highest studied dose Dose: 3600 mg, 1 times / day Route: oral Route: multiple Dose: 3600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/
Anxiety	16.7% Disc. AE	2400 mg 1 times / day multiple, oral Studied dose Dose: 2400 mg, 1 times / day Route: oral Route: multiple Dose: 2400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/
Diarrhea	16.7% Disc. AE	2400 mg 1 times / day multiple, oral Studied dose Dose: 2400 mg, 1 times / day Route: oral Route: multiple Dose: 2400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/
Headache	16.7% Disc. AE	2400 mg 1 times / day multiple, oral Studied dose Dose: 2400 mg, 1 times / day Route: oral Route: multiple Dose: 2400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/
Myalgia	16.7% Disc. AE	2400 mg 1 times / day multiple, oral Studied dose Dose: 2400 mg, 1 times / day Route: oral Route: multiple Dose: 2400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/
Vomiting	16.7% Disc. AE	2400 mg 1 times / day multiple, oral Studied dose Dose: 2400 mg, 1 times / day Route: oral Route: multiple Dose: 2400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/24535888/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252 supressor 22	inhibitor 2438 substrate 1193	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A5 136 OAT3 747 MATE2-K 77 OCT2 779 CYP2C19 2057 MATE1 415 OAT1 725 CYP1A2 2153 CYP2B6 926 OATP1B1 1079 CYP2C8 1057 BCRP 910 OATP1B3 961 P-gp 1741 OCT1 620	FMO1 25 CYP2B6 776 CYP2C8 810 CYP1A2 1197 P-gp 2052 FMO5 5 CYP4F2 11 CYP2J2 71 FMO3 77 CYP1A1 389 CYP2A6 626 CYP2C19 1119 CYP3A5 446	CYP2B6 669 CYP1A2 832

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 209.0	no [IC50 >100 uM]
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 209.0	no [IC50 >251 uM]	Fexinidazole sulfoxide 1
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 209.0	no [IC50 >251 uM]	Fexinidazole sulfoxide 1
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 209.0	no [IC50 >300 uM]	Fexinidazole sulfone 1
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 213.0	no [IC50 >302 uM]	Fexinidazole sulfone 1
CYP3A5 201	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 213.0	no [IC50 >302 uM]	Fexinidazole sulfone 1
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 209.0	no [IC50 >353 uM]	Fexinidazole sulfone 1
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 209.0	no
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 99 \| 214	no	Fexinidazole sulfone 1
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 99 \| 214	no	Fexinidazole sulfoxide 1
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 99 \| 214	no	Fexinidazole sulfone 1
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 84 \| 88 \| 91 \| 97 \| 98 \| 213	yes [IC50 0.863 uM]		yes (co-administration study) Comment: Fexinidazole increased omeprazole AUC by 2.1-fold and Cmax by 2.0-fold. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 84 \| 88 \| 91 \| 97 \| 98 \| 213
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 91 \| 97 \| 213	yes [IC50 10.8 uM]	Fexinidazole sulfoxide 1
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 88 \| 91 \| 100 \|209	yes [IC50 113 uM]	Fexinidazole sulfoxide 1
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 97 \| 213	yes [IC50 118 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 91 \| 100 \| 209	yes [IC50 121 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 97 \| 213	yes [IC50 142 uM]	Fexinidazole sulfoxide 1
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 97 \| 213	yes [IC50 147 uM]
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 88 \| 91 \| 100 \|209	yes [IC50 18.1 uM]	Fexinidazole sulfone 1
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 85 \| 88 \| 91 \| 100 \| 209	yes [IC50 2.08 uM]
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 88 \| 91 \| 100 \| 209	yes [IC50 202 uM]	Fexinidazole sulfone 1
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 209.0	yes [IC50 203 uM]	Fexinidazole sulfone 1
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 84 \| 88 \| 91 \| 97 \| 98 \| 213	yes [IC50 22.3 uM]		yes (co-administration study) Comment: Fexinidazole increased caffeine AUC by 2.1-fold and Cmax by 1.2-fold. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 84 \| 88 \| 91 \| 97 \| 98 \| 213
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 91 \| 97 \| 213	yes [IC50 26.5 uM]
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 85 \| 88 \| 91 \| 100 \| 209	yes [IC50 267 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 97 \| 213	yes [IC50 278 uM]	Fexinidazole sulfoxide 1
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 209.0	yes [IC50 281 uM]	Fexinidazole sulfoxide 1
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 100 \| 209	yes [IC50 282 uM]	Fexinidazole sulfone 1
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 85 \| 88 \| 91 \| 100 \| 209	yes [IC50 33.5 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 84 \| 91 \| 97 \| 213	yes [IC50 35.4 uM]
CYP3A5 201	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 91 \| 97 \| 213	yes [IC50 35.4 uM]
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 85 \| 88 \| 91 \| 100 \|209	yes [IC50 38.9 uM]
MATE2-K 77	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 88 \| 91 \| 100 \|209	yes [IC50 39.3 uM]	Fexinidazole sulfone 1
MATE2-K 77	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 85 \| 88 \| 91 \| 100 \| 209	yes [IC50 4.38 uM]
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 88 \| 91 \| 100 \|209	yes [IC50 44.3 uM]	Fexinidazole sulfone 1
MATE2-K 77	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 88 \| 91 \| 100 \|209	yes [IC50 44.9 uM]	Fexinidazole sulfoxide 1
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 88 \| 91 \| 100 \|209	yes [IC50 53.9 uM]	Fexinidazole sulfoxide 1
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 91 \| 100 \| 209	yes [IC50 68.7 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 91 \| 100 \| 209	yes [IC50 69.8 uM]
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 88 \| 91 \| 100 \|209	yes [IC50 71.8 uM]	Fexinidazole sulfone 1
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 91 \| 213	yes [IC50 98.5 uM]
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 99 \| 214	yes
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 85 \| 91 \| 99 \| 214	yes
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 91.0	yes	Fexinidazole sulfoxide 1
CYP3A4 2633	supressor 160 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 214.0	yes
CYP3A4 2633	supressor 160 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 214.0	yes	Fexinidazole sulfone 1
CYP3A4 2633	supressor 160 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 214.0	yes	Fexinidazole sulfoxide 1

Drug as victim

Target	Modality	Activity	Metabolite
CYP2B6 776	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 199 \| 202	no
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 199.0	weak
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 199 \| 202	weak
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 199 \| 202	weak
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 207.0	weak
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 207.0	weak	Fexinidazole sulfone 1
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 207.0	weak	Fexinidazole sulfoxide 1
CYP1A1 389	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 202.0	yes
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 199 \| 202	yes
CYP2A6 626	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 202.0	yes
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 199 \| 202	yes
CYP2J2 71	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 202.0	yes
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 88 \| 90 \| 199 \| 202	yes
CYP3A5 446	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 199 \| 202	yes
CYP4F2 11	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 202.0	yes
FMO1 25	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 88 \| 90 \| 202	yes
FMO3 77	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 88 \| 90 \| 202	yes
FMO5 5	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 88 \| 90 \| 202	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214429Orig1s000MultidisciplineR.pdf Page: 57.0		Fexinidazole sulfone 1

PubMed

Title	Date	PubMed
The anti-tubercular drug delamanid as a potential oral treatment for visceral leishmaniasis.	2016-05-24	27215734
The anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis.	2012-02-01	22301556
Fexinidazole--a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness.	2010-12-21	21200426
The activity of fexinidazole (HOE 239) against experimental infections with Trypanosoma cruzi, trichomonads and Entamoeba histolytica.	1983-02	6411009

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 Created by `admin` on `Mon Mar 31 18:45:10 GMT 2025` Edited by `admin` on `Mon Mar 31 18:45:10 GMT 2025`
Record UNII	306ERL82IR
Record Status	`Validated (UNII)`
Record Version

Download

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

1H-IMIDAZOLE, 1-METHYL-2-((4-(METHYLTHIO)PHENOXY)METHYL)-5-NITRO-

Systematic Name

English

FEXINIDAZOLE [USAN]

Common Name

English

FEXINIDAZOLE [ORANGE BOOK]

Common Name

English

Fexinidazole [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C277