IOWH-032

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H15Br2N3O4
Molecular Weight	545.18
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=C(Br)C=C(C=C1Br)C2=NOC(=N2)C(=O)NCC3=CC=C(OC4=CC=CC=C4)C=C3

InChI

InChIKey=DSFNLJXHXBIKDS-UHFFFAOYSA-N

InChI=1S/C22H15Br2N3O4/c23-17-10-14(11-18(24)19(17)28)20-26-22(31-27-20)21(29)25-12-13-6-8-16(9-7-13)30-15-4-2-1-3-5-15/h1-11,28H,12H2,(H,25,29)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27288484
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800037066 | https://www.ncbi.nlm.nih.gov/pubmed/21859305 | doi:10.1016/S0016-5085(14)62292-7 | https://www.ncbi.nlm.nih.gov/pubmed/24551253

IOWH032 is a synthetic extracellular CFTR inhibitor, originally developed to treat diarrhea, that entered Phase II clinical trials in 2013 but did not progress further in clinical development. iOWH032 has low CFTR inhibition potency (IC50 > 5 uM) and hence rapid (seconds or less) dissociation from CFTR. iOWH032 inhibited secretion by nearly 70% as measured on a semi-quantitative fecal output scale.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cystic fibrosis transmembrane conductance regulator 6 Target ID: CHEMBL4051 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24551253	Inhibitor 8297		5.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cholera 7 Sources: DOI: 10.1016/S0016-5085(14)62292-7 https://www.ncbi.nlm.nih.gov/pubmed/24551253 https://www.ncbi.nlm.nih.gov/pubmed/21859305	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1280 ng/mL OTHER https://path.azureedge.net/media/documents/DD_ddw_pstr.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		IOWH-032 plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
482 ng/mL OTHER https://path.azureedge.net/media/documents/DD_ddw_pstr.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		IOWH-032 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
22700 ng × h/mL OTHER https://path.azureedge.net/media/documents/DD_ddw_pstr.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		IOWH-032 plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
6250 ng × h/mL OTHER https://path.azureedge.net/media/documents/DD_ddw_pstr.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		IOWH-032 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.5 h OTHER https://path.azureedge.net/media/documents/DD_ddw_pstr.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		IOWH-032 plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
8.2 h OTHER https://path.azureedge.net/media/documents/DD_ddw_pstr.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		IOWH-032 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P000PMC	https://www.1pchem.com/search?query=1P000PMC
AK Scientific	2156AH	https://aksci.com/item_detail.php?cat=2156AH
AOBIOUS INC	AOB87123	http://aobious.com/aobious/search?search_query=AOB87123
Angene	AGN-PC-0WAGLU	http://www.angenechemical.com/productshow/AGN-PC-0WAGLU.html
AstaTech	44058	http://astatechinc.com/CPSResult.php?CRNO=44058
Chem Scene	CS-1744	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1744
ChemShuttle	111962	https://www.chemshuttle.com/catalogsearch/result/?q=111962
Combi-Blocks	QJ-3015	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-3015
Excenen	EX-A327	http://www.excenen.com/searchresultlist.php?id=EX-A327
KeyOrganics	AS-74457	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-74457
Matrix Scientific	147281	http://www.matrixscientific.com/147281.html
MedChem Express	HY-18337	https://www.medchemexpress.com/search.html?q=HY-18337&ft=&fa=&fp=
MolPort	MolPort-035-395-840	https://www.molport.com/shop/molecule-link/MolPort-035-395-840
Molnova	M10658	https://www.molnova.com/en/serch-list.html?keywords=M10658
Selleck Chemicals	S7329	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7329
ShangHai Biochempartner	BCP001041	http://www.biochempartner.com/search_BCP001041
ShangHai Biochempartner	BCP08439	http://www.biochempartner.com/search_BCP08439
TargetMol	T2486	https://www.targetmol.com/search?keyword=T2486
eMolecules	49383490	https://orderbb.emolecules.com/search/#?query=49383490
eNovation Chemicals	D372351	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D372351&searchbtn.x=0&searchbtn.y=0

PubMed

Title	Date	PubMed
Developing novel antisecretory drugs to treat infectious diarrhea.	2011 Aug	21859305
Antidiarrheal efficacy and cellular mechanisms of a Thai herbal remedy.	2014 Feb	24551253
Potentiators exert distinct effects on human, murine, and Xenopus CFTR.	2016 Aug 1	27288484

Patents

Sample Use Guides

In Vivo Use Guide

Single dose of 300 mg

Route of Administration: Oral

In Vitro Use Guide

IOWH-032 rapidly blocked and potentiated hCFTR activity in a concentration-dependent manner with apparent Kd value of 6.1 nM and 0.64 nM, respectively. However, IOWH-032 did not potentiate and only blocked mCFTR with an apparent Kd value of 42.9 uM.

Name

Type

Language

IOWH-032

Common Name

English

1,2,4-OXADIAZOLE-5-CARBOXAMIDE, 3-(3,5-DIBROMO-4-HYDROXYPHENYL)-N-((4-PHENOXYPHENYL)METHYL)-

Systematic Name

English

IOWH032

Common Name

English

Code System Code Type Description

DRUG BANK

DB12959