307510-92-5 Usage
Description
CFTRinh-172, also known as CFTR Inhibitor-172, is a thiazolidinone compound that selectively blocks the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) channel in a voltage-independent manner. It directly modulates the gating of chloride at the channel without affecting the elevation of cAMP or inhibiting other pumps or channels. CFTRinh-172 is a promising pharmaceutical candidate for the treatment of cystic fibrosis and related conditions.
Uses
Used in Pharmaceutical Industry:
CFTRinh-172 is used as a specific inhibitor for the cystic fibrosis transmembrane conductance regulator (CFTR) activity. It is particularly effective in treating conditions where CFTR channel dysfunction is a contributing factor, such as cystic fibrosis and polycystic kidney disease.
Used in Research Applications:
CFTRinh-172 is used as a CFTR inhibitor in research settings to study the role of CFTR in various biological processes. It is employed in experiments involving forskolin and IBMX, which are compounds that activate adenylate cyclase and increase cAMP levels, leading to the activation of CFTR channels.
Additionally, CFTRinh-172 can be used to investigate the effects of CFTR modulation on intracellular glutathione (GSH) concentration and reactive oxygen species balance, as CFTR also plays a role in regulating GSH efflux.
Biological Activity
Voltage-independent, selective CFTR chloride channel blocker (K i = 300 nM) that alters channel gating. Blocks intestinal fluid secretion induced by cholera toxin and Escherichia coli and suppresses cyst growth in animal models of polycystic kidney disease. Orally active. Inhibits mitochondrial respiration and increases reactive oxygen species (ROS) production independently of CFTR in several cell lines.
Biochem/physiol Actions
CFTR(inh)-172 is an inhibitor of the cystic fibrosis transmembrane conductance regulator (CFTR). With a Ki = 300 nM,. CFTR(inh)-172 leads to rapid, reversible and voltage-independent inhibition; it is an antidiarrheal agent in animals. CTFR(inh)-172 may be a useful tool to study animal models of cystic fibrosis and intestinal fluid loss in cholera and other secretory diarrheas. CTFR(inh)-172 is structurally-unrelated to known, but non-specific CFTR inhibitors DPC, NPPB (Cat. No. N4779) and Glibenclamide.
in vitro
cftrinh-172 could reversibly inhibit cftr short-circuit current in less than 2 minutes in a voltage-independent manner. moreover, at concentrations fully inhibiting cftr, cftrinh-172 did not prevent elevation of cellular camp or inhibit non-cftr cl–channels, multidrug resistance protein-1, atp-sensitive k+ channels, or a series of other transporters [2].
in vivo
a single ip injection of cftrinh-172 (250 μg/kg) in mice reduced by more than 90% cholera toxin–induced fluid secretion in the small intestine over 6 hours. cftrinh-172 may be useful in developing large-animal models of cystic fibrosis and reducing intestinal fluid loss in cholera and other secretory diarrheas [3].
references
[1] ma t, thiagarajah jr, yang h, sonawane nd, folli c, galietta lj, verkman as. thiazolidinone cftr inhibitor identified by high-throughput screening blocks cholera toxin-induced intestinal fluid secretion. j clin invest. 2002 dec;110(11):1651-8.
Check Digit Verification of cas no
The CAS Registry Mumber 307510-92-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,0,7,5,1 and 0 respectively; the second part has 2 digits, 9 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 307510-92:
(8*3)+(7*0)+(6*7)+(5*5)+(4*1)+(3*0)+(2*9)+(1*2)=115
115 % 10 = 5
So 307510-92-5 is a valid CAS Registry Number.
InChI:InChI=1/C18H10F3NO3S2/c19-18(20,21)12-2-1-3-13(9-12)22-15(23)14(27-17(22)26)8-10-4-6-11(7-5-10)16(24)25/h1-9H,(H,24,25)/b14-8+
307510-92-5Relevant articles and documents
Thiazolinone heterocyclic compound, preparation method, medicinal composition and application thereof
-
Paragraph 0193; 0195; 0219; 0220; 0222, (2019/01/09)
The invention provides a thiazolinone heterocyclic compound, a preparation method, a medicinal composition and an application thereof. The invention provides an application of the thiazolinone heterocyclic compound in preparation of an NLRP3 inflammasome inhibitor. The thiazolinone heterocyclic compound has a structure as a formula I or an isomer, a prodrug, or a pharmaceutically acceptable solvate or salt thereof.
Thiazolidinone CFTR inhibitors with improved water solubility identified by structure-activity analysis
Sonawane,Verkman
experimental part, p. 8187 - 8195 (2009/04/11)
The thiazolidinone 3-[(3-trifluoromethyl)phenyl]-5-[(4-carboxyphenyl)methylene]-2-thioxo-4-thiazolidinone (CFTRinh-172) inhibits cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel conductance with submicromolar affinity and blocks cholera toxin-induced intestinal fluid secretion. Fifty-eight CFTRinh-172 analogs were synthesized to identify CFTR inhibitors with improved water solubility, exploring modifications in its two phenyl rings, thiazolidinone core, and core-phenyl connectors. Greatest CFTR inhibition potency was found for 3-CF3 and polar group-substituted-phenyl rings, and a thiazolidinone core. Two compounds with ～1 μM CFTR inhibition potency and solubility >180 μM (>10-fold more than CFTRinh-172) were identified: Tetrazolo-172, containing 4-tetrazolophenyl in place of 4-carboxyphenyl, and Oxo-172, containing thiazolidinedione in place of the thiazolidinone core. These water soluble thiazolidinone analogs had low cellular toxicity. The improved water solubility of Tetrazolo- and Oxo-172 make them potential lead candidates for therapy of secretory diarrheas and polycystic kidney disease.
