1191252-49-9

Basic information

• Product Name: iOWH-032
• Synonyms: 1,2,4-Oxadiazole-5-carboxamide, 3-(3,5-dibromo-4-hydroxyphenyl)-N-[(4-phenoxyphenyl)methyl]-;3-(3,5-Dibromo-4-hydroxyphenyl)-N-[(4-phenoxyphenyl)methyl]-1,2,4-oxadiazole-5-carboxamide IOWH032;iOWH-032;3-(3,5-Dibromo-4-hydroxyphenyl)-N-[(4-phenoxyphenyl)methyl]-1,2,4-oxadiazole-5-carboxamide;3-(3,5-DibroMo-4-hydroxyphenyl)-N-(4-phenoxybenzyl)-1,2,4-oxadiazole-5-carboxaMide
• CAS NO: 1191252-49-9
• Molecular Formula: C22H15Br2N3O4
• Molecular Weight: 545.1802
• Product Categories: Inhibitors
• Mol File: 1191252-49-9.mol
• Article Data: 2

Chemical Properties

• Appearance: /
• Density: 1.670±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• Solubility: ≥21.85 mg/mL in DMSO; insoluble in H2O; ≥3.13 mg/mL in EtOH with gentle warming
• PKA: 3.34±0.46(Predicted)
• CAS DataBase Reference: iOWH-032(CAS DataBase Reference)
• NIST Chemistry Reference: iOWH-032(1191252-49-9)
• EPA Substance Registry System: iOWH-032(1191252-49-9)

Safety Data

• Hazardous Substances Data: 1191252-49-9(Hazardous Substances Data)

Usage

Description

IOWH032 is a synthetic CFTR inhibitor with IC50 of 1.01 μM in CHO-CFTR cell based assays. Phase 2.

In vitro

IOWH032 shows inhibitory activity against CFTR in T84-CFTR cell based assays with IC50 of 6.87 μM.

In vivo

In a mouse closed-loop model, IOWH032 causes a statistical significant inhibition against cholera toxin (CTX) induced secretion. IOWH032 (5 mg/kg) reduces the fecal output index by ~70% in a cecetomized rat model.

Uses

IOWH032 is a synthetic?cystic fibrosis transmembrane conductance regulator (CFTR) ?inhibitor.

Biological Activity

iowh-032 is a potent and synthetic extracellular cystic fibrosis transmembrane conductance regulator (cftr) inhibitor with ic50 value of 1.01 μm in t84 and cho-cftr cell based assays [1]. the cftr chloride channel is the most attractive because it is the primary driver of secretion in cases of diarrhea caused by enterotoxigenic bacteria. cftr plays an important role in transepithelial fluid homeostasis through controlling the flow of chloride ions and thus the movement of water in and out of cells [1].

in vitro

iowh032 inhibited cftr activity with ic50 value of 6.87 μm in t84-cftr cell based assays [1]. 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 μm [2].

in vivo

iowh032 significantly inhibited cholera toxin (ctx)-induced secretion in a mouse closed-loop model. moreover, iowh032 (5 mg/kg, po dose) decreased the fecal output index by apparent 70% compared to vehicle (cholera toxin) in a cecetomized rat model. iowh032 inhibited cftr activity with ic50 value of 6.87 μm in t84-cftr cell based assays [1].

target

cftr

IC 50

1.01 μm

references

1. doyle k, et al. inhibitors of the cftr chloride ion channel as potential treatment for acute secretory diarrhea: development of 5-membered heterocycles suitable for pre-clinical evaluation.1. de hostos el, choy rk, nguyen t. developing novel antisecretory drugs to treat infectious diarrhea. future med chem. 2011;3(10):1317-25. 2. cui g, khazanov n, stauffer b, infield dt, imhoff br, senderowitz h, et al. potentiators exert distinct effects on human, murine, and xenopus cftr. am j physiol lung cell mol physiol. 2016:ajplung 00056 2016.

Downstream Products

• 1421276-01-8 C₃₀H₃₂Br₂N₃O₇P 
• 1421275-99-1 C₃₁H₃₄Br₂N₃O₈P 

Relevant articles and documents

Compounds, Compositions and Methods Comprising Oxadiazole Derivatives

The present invention relates to compositions and methods for treating a disease in an animal, which disease is responsive to inhibiting of functional cystic fibrosis transmembrane conductance regulator (CFTR) polypeptide by administering to a mammal in n