1191252-49-9 Usage
Uses
Used in Pharmaceutical Industry:
iOWH-032 is used as a CFTR inhibitor for the treatment of cystic fibrosis. It works by inhibiting the CFTR protein, which is responsible for regulating the flow of chloride ions across cell membranes. This inhibition can help to reduce the thick mucus buildup that is characteristic of cystic fibrosis, thereby improving lung function and overall quality of life for patients.
Used in Research Applications:
iOWH-032 is also used as a research tool for studying the role of CFTR in various cellular processes and diseases. Its ability to inhibit CFTR makes it a valuable compound for investigating the molecular mechanisms underlying cystic fibrosis and other related conditions. Additionally, it can be used to screen for potential new therapeutic agents that target the CFTR protein.
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.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 1191252-49-9 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,1,9,1,2,5 and 2 respectively; the second part has 2 digits, 4 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 1191252-49:
(9*1)+(8*1)+(7*9)+(6*1)+(5*2)+(4*5)+(3*2)+(2*4)+(1*9)=139
139 % 10 = 9
So 1191252-49-9 is a valid CAS Registry Number.
1191252-49-9Relevant academic research and scientific papers
Compounds, Compositions and Methods Comprising Oxadiazole Derivatives
-
Page/Page column 106, (2009/10/30)
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
Compounds, Compositions and Methods Comprising Heteroaromatic Derivatives
-
Page/Page column 246, (2009/12/28)
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 need thereof an effective amount of a compound defined herein (including those compounds set forth in Tables 1-14 or encompassed by formulas I-XII) or compositions thereof, thereby treating the disease. The present invention particularly, relates to a method of treating diarrhea and polycystic kidney disease.
