4-AMINO-N-(3-CHLORO-4-FLUOROPHENYL)-N'-HYDROXY-1,2,5-OXADIAZOLE-3-CARBOXIMIDAMIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H7ClFN5O2
Molecular Weight	271.636
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure of 4-AMINO-N-(3-CHLORO-4-FLUOROPHENYL)-N'-HYDROXY-1,2,5-OXADIAZOLE-3-CARBOXIMIDAMIDE

Structure Search

SMILES

NC1=NON=C1\C(NO)=N\C2=CC(Cl)=C(F)C=C2

InChI

InChIKey=HGXSLPIXNPASGZ-UHFFFAOYSA-N

InChI=1S/C9H7ClFN5O2/c10-5-3-4(1-2-6(5)11)13-9(14-17)7-8(12)16-18-15-7/h1-3,17H,(H2,12,16)(H,13,14)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27192116 | https://www.ncbi.nlm.nih.gov/pubmed/26990117
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20197554

4-Amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide (Epacadostat) is an orally available hydroxyamidine and inhibitor of indoleamine 2,3-dioxygenase (IDO1), with potential immunomodulating and antineoplastic activities. epacadostat targets and binds to IDO1, an enzyme responsible for the oxidation of tryptophan into kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, epacadostat increases and restores the proliferation and activation of various immune cells, including dendritic cells (DCs), NK cells, and T-lymphocytes, as well as interferon (IFN) production, and a reduction in tumor-associated regulatory T cells (Tregs). Activation of the immune system, which is suppressed in many cancers, may inhibit the growth of IDO1-expressing tumor cells. IDO1 is overexpressed by a variety of tumor cell types and DCs. Epacadostat is in clinical development as a novel orally active immuno-oncological therapy.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Indoleamine 2,3-dioxygenase 19 Target ID: CHEMBL4685 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26990117 \| https://www.ncbi.nlm.nih.gov/pubmed/20197554	Inhibitor 8297		10.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Melanoma 88 Sources: https://clinicaltrials.gov/ct2/show/NCT02752074	Primary	Phase III 656	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: https://clinicaltrials.gov/ct2/show/NCT02575807	Primary	Phase II 1132	Unknown Approved Use Unknown
Peritoneal cancer 11 Sources: https://clinicaltrials.gov/ct2/show/NCT02575807	Primary	Phase II 1132	Unknown Approved Use Unknown
Fallopian tube cancer 17 Sources: https://clinicaltrials.gov/ct2/show/NCT02575807	Primary	Phase II 1132	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: https://clinicaltrials.gov/ct2/show/NCT02318277	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
6.23 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28053021	700 mg 2 times / day steady-state, oral dose: 700 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		4-AMINO-N-(3-CHLORO-4-FLUOROPHENYL)-N'-HYDROXY-1,2,5-OXADIAZOLE-3-CARBOXIMIDAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
35.8 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28053021	700 mg 2 times / day steady-state, oral dose: 700 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		4-AMINO-N-(3-CHLORO-4-FLUOROPHENYL)-N'-HYDROXY-1,2,5-OXADIAZOLE-3-CARBOXIMIDAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28053021	700 mg 2 times / day steady-state, oral dose: 700 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		4-AMINO-N-(3-CHLORO-4-FLUOROPHENYL)-N'-HYDROXY-1,2,5-OXADIAZOLE-3-CARBOXIMIDAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
700 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 4 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	Other AEs: Abdominal pain, Weight decreased... Other AEs: Abdominal pain (all grades, 25%) Weight decreased (all grades, 25%) Fatigue (grades 3-4, 25%) Decreased appetite (all grades, 75%) Dyspnea (all grades, 25%) Constipation (all grades, 75%) Hypokalemia (grades 3-4, 25%) Dizziness (all grades, 25%) pain (all grades, 50%) Vomiting (all grades, 50%) Back pain (all grades, 50%) Diarrhea (all grades, 25%) Dysgeusia (all grades, 25%) Nausea (all grades, 75%) Sources: https://pubmed.ncbi.nlm.nih.gov/28053021
100 mg 2 times / day multiple, oral (unknown) Studied dose Dose: 100 mg, 2 times / day Route: oral Route: multiple Dose: 100 mg, 2 times / day Co-administed with:: pembrolizumab(200 mg intravenously (IV) Q3W) Sources: https://pubmed.ncbi.nlm.nih.gov/32564277	unhealthy n = 6 Health Status: unhealthy Condition: advanced solid tumors Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/32564277	DLT: habdomyolysis... Dose limiting toxicities: habdomyolysis (grade 4, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/32564277
300 mg 2 times / day multiple, oral (unknown) Studied dose Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 6 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	DLT: Radiation pneumonit... Dose limiting toxicities: Radiation pneumonit (grade 3, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/28053021
400 mg 2 times / day multiple, oral (unknown) Studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 11 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	DLT: Fatigue... Dose limiting toxicities: Fatigue (grade 3, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/28053021

AEs

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00GUKF	https://www.1pchem.com/search?query=1P00GUKF
A2B Chem	AH85311	http://a2bchem.com/prod/AH85311
AChemBlock	10341	http://www.achemblock.com/catalogsearch/result/?q=10341
AOBIOUS INC	AOB6408	http://aobious.com/aobious/search?search_query=AOB6408
Aceschem	ACF022732	https://www.aceschem.com/catalog/search.do?q=ACF022732
Achemo Scientific Limited	AC-107850	http://www.achemo.com/search/?Keyword=AC-107850
Ambeed	A165598	http://www.ambeed.com/search/Search.html?keyword=A165598
Angene	AGN-PC-0WAHUX	http://www.angenechemical.com/productshow/AGN-PC-0WAHUX.html
AstaTech	41432	http://astatechinc.com/CPSResult.php?CRNO=41432
AstaTech	42505	http://astatechinc.com/CPSResult.php?CRNO=42505
Axon MedChem	2215	https://www.axonmedchem.com/product/2215
BLD Pharm	BD302773	http://www.bldpharm.com/search/Search.html?keyword=BD302773
Cayman Chemical	18265	http://www.caymanchem.com/app/template/Product.vm/catalog/18265
ChemShuttle	112013	https://www.chemshuttle.com/catalogsearch/result/?q=112013
Combi-Blocks	QV-6520	http://www.combi-blocks.com/cgi-bin/find.cgi?QV-6520
Enamine	EN300-747103	https://www.enaminestore.com/catalog/EN300-747103
Excenen	EX-A2076	http://www.excenen.com/searchresultlist.php?id=EX-A2076
KeyOrganics	AS-35126	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-35126
Lab Network	LN01298170	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01298170
Matrix Scientific	147319	http://www.matrixscientific.com/147319.html
MedChem Express	HY-15683	https://www.medchemexpress.com/search.html?q=HY-15683&ft=&fa=&fp=
MolPort	MolPort-009-680-335	https://www.molport.com/shop/molecule-link/MolPort-009-680-335
MolPort	MolPort-035-789-702	https://www.molport.com/shop/molecule-link/MolPort-035-789-702
MolPort	MolPort-038-357-371	https://www.molport.com/shop/molecule-link/MolPort-038-357-371
MolPort	MolPort-038-357-372	https://www.molport.com/shop/molecule-link/MolPort-038-357-372
MolPort	MolPort-039-137-139	https://www.molport.com/shop/molecule-link/MolPort-039-137-139
MuseChem	I005831	https://www.musechem.com/product/I005831.html
Otava	7862388	https://search.otavachemicals.com/#!/search?query=7862388&type=code
Ryan Scientific	101-94174	https://ryansci.com/products?q=101-94174&list_q=&search_type=exact
Selleck Chemicals	S7587	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7587
ShangHai Biochempartner	BCP001045	http://www.biochempartner.com/search_BCP001045
ShangHai Biochempartner	BCP08453	http://www.biochempartner.com/search_BCP08453
Synthonix	SL100240	http://www.synthon-lab.com/search.php?cas_or_id=SL100240&cas_id_field=1
TargetMol	T2647	https://www.targetmol.com/search?keyword=T2647
Toronto Research Chemicals	I499600	https://www.trc-canada.com/product-detail/?CatNum=I499600
eMolecules	43677058	https://orderbb.emolecules.com/search/#?query=43677058
eMolecules	49837423	https://orderbb.emolecules.com/search/#?query=49837423
eMolecules	50280772	https://orderbb.emolecules.com/search/#?query=50280772
eMolecules	54823071	https://orderbb.emolecules.com/search/#?query=54823071
eMolecules	60180635	https://orderbb.emolecules.com/search/#?query=60180635
mcule	MCULE-2253204487	https://mcule.com/MCULE-2253204487/

PubMed

Title	Date	PubMed
Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity.	2010 Apr 29	20197554
The IDO1 selective inhibitor epacadostat enhances dendritic cell immunogenicity and lytic ability of tumor antigen-specific T cells.	2016 Jun 21	27192116
Potential Underprediction of Warfarin Drug Interaction From Conventional Interaction Studies and Risk Mitigation: A Case Study With Epacadostat, an IDO1 Inhibitor.	2016 Nov	26990117

Patents

Sample Use Guides

In Vivo Use Guide

4-Amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide (Epacadostat) 25 mg BID as starting dose

Route of Administration: Oral

In Vitro Use Guide

4-Amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide ( (1.0 uM)) significantly decreased Treg proliferation induced by IDO production from IFN-γ plus LPS matured human DCs

Name

Type

Language

4-AMINO-N-(3-CHLORO-4-FLUOROPHENYL)-N'-HYDROXY-1,2,5-OXADIAZOLE-3-CARBOXIMIDAMIDE

Systematic Name

English

1,2,5-OXADIAZOLE-3-CARBOXIMIDAMIDE, 4-AMINO-N'-(3-CHLORO-4-FLUOROPHENYL)-N-HYDROXY-

Systematic Name

English

1,2,5-OXADIAZOLE-3-CARBOXIMIDAMIDE, 4-AMINO-N-(3-CHLORO-4-FLUOROPHENYL)-N'-HYDROXY-

Systematic Name

English

Code System Code Type Description

CAS

914471-09-3

Created by admin on Sat Dec 16 10:57:38 GMT 2023 , Edited by admin on Sat Dec 16 10:57:38 GMT 2023

PRIMARY

FDA UNII

2HR315841W

Created by admin on Sat Dec 16 10:57:38 GMT 2023 , Edited by admin on Sat Dec 16 10:57:38 GMT 2023

PRIMARY

PUBCHEM

135424953

Created by admin on Sat Dec 16 10:57:38 GMT 2023 , Edited by admin on Sat Dec 16 10:57:38 GMT 2023

PRIMARY

ACTIVE MOIETY


					2HR315841W

4-AMINO-N-(3-CHLORO-4-FLUOROPHENYL)-N'-HYDROXY-1,2,5-OXADIAZOLE-3-CARBOXIMIDAMIDE

AE	Significance	Dose	Population
Abdominal pain	all grades, 25%	700 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 4 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021
Diarrhea	all grades, 25%	700 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 4 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021
Dizziness	all grades, 25%	700 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 4 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021
Dysgeusia	all grades, 25%	700 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 4 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021
Dyspnea	all grades, 25%	700 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 4 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021
Weight decreased	all grades, 25%	700 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 4 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021
Back pain	all grades, 50%	700 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 4 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021
Vomiting	all grades, 50%	700 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 4 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021
pain	all grades, 50%	700 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 4 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021
Constipation	all grades, 75%	700 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 4 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021
Decreased appetite	all grades, 75%	700 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 4 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021
Nausea	all grades, 75%	700 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 4 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021
Fatigue	grades 3-4, 25%	700 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 4 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021
Hypokalemia	grades 3-4, 25%	700 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 4 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021
habdomyolysis	grade 4, 1 pt DLT, Disc. AE	100 mg 2 times / day multiple, oral (unknown) Studied dose Dose: 100 mg, 2 times / day Route: oral Route: multiple Dose: 100 mg, 2 times / day Co-administed with:: pembrolizumab(200 mg intravenously (IV) Q3W) Sources: https://pubmed.ncbi.nlm.nih.gov/32564277	unhealthy n = 6 Health Status: unhealthy Condition: advanced solid tumors Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/32564277
Radiation pneumonit	grade 3, 1 pt DLT	300 mg 2 times / day multiple, oral (unknown) Studied dose Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 6 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021
Fatigue	grade 3, 1 pt DLT	400 mg 2 times / day multiple, oral (unknown) Studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28053021	unhealthy n = 11 Health Status: unhealthy Condition: Advanced Solid Malignancies Sex: M+F Food Status: FASTED Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/28053021

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/27192116 | https://www.ncbi.nlm.nih.gov/pubmed/26990117Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20197554

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Approved Use

Approved Use

Approved Use

Cmax

AUC

T1/2

Doses

AEs

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27192116 | https://www.ncbi.nlm.nih.gov/pubmed/26990117
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20197554

C_max

T_1/2