Disease relevance of GW0072

• Thiazolidinone CFTR inhibitors may be useful in developing large-animal models of cystic fibrosis and in reducing intestinal fluid loss in cholera and other secretory diarrheas [1].

High impact information on GW0072

• Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin-induced intestinal fluid secretion [1].
• A thiazolidinone-type CFTR blocker (CFTR(inh)-172) reduced cholera toxin-induced fluid accumulation in mouse intestinal loops [2].
• Modifications of cellulose synthase confer resistance to isoxaben and thiazolidinone herbicides in Arabidopsis Ixr1 mutants [3].
• X-ray crystallography revealed that GW0072 occupied the ligand-binding pocket by using different epitopes than the known PPAR agonists and did not interact with the activation function 2 helix [4].
• In cell culture, GW0072 was a potent antagonist of adipocyte differentiation [4].

Biological context of GW0072

• GW0072 was identified as a high-affinity PPARgamma ligand that was a weak partial agonist of PPARgamma transactivation [4].
• Novel calcium antagonists with both calcium overload inhibition and antioxidant activity. 2. Structure-activity relationships of thiazolidinone derivatives [5].

Anatomical context of GW0072

• Recently a new anion channel inhibitor, a thiazolidinone derivative, termed CFTRInh-172 has been synthesized and introduced with apparently improved inhibitory properties as shown by effects on anion conductance expressed in cell lines and on secretion in vivo [6].
• Thiazolidinone congeners as central nervous system active agents [7].

Associations of GW0072 with other chemical compounds

• Semidominant mutations at the IXR1 and IXR2 loci of Arabidopsis confer isoxaben and thiazolidinone resistance [3].
• The divergent effects of PPAR gamma 2 ligands on osteoblast and adipocyte differentiation were confirmed in primary murine bone marrow cultures using rosiglitazone and GW0072 [8].
• High-throughput screening of small molecule collections utilizing a cell-based fluorescence assay of halide transport yielded thiazolidinone and glycine hydrazide CFTR inhibitors that block enterotoxin-mediated secretory diarrhea in rodent models, including a class of non-absorbable inhibitors that target the CFTR pore at its external entrance [9].
• Ralitoline, a thiazolidinone derivative chemically distinct from known antiepileptic drugs, possesses remarkable anticonvulsant properties as demonstrated in various animal models of epilepsy [10].
• Three of five obtained analogues, pyrrolidinone, oxazolidinone and thiazolidinone demonstrated an interesting, specific odor which was compared with floral, typical jasmine odor of jasmone [11].

Gene context of GW0072

• Altered channel gating mechanism for CFTR inhibition by a high-affinity thiazolidinone blocker [12].
• We used the selective thiazolidinone CFTR inhibitor CFTR(inh)-172 to define the involvement of CFTR in nasal PD changes in mice and pigs [13].
• By screening unbiased combinatorial chemistry libraries, using a cAMP-responsive luciferase reporter assay, we discovered thiazolidinone agonists (EC(50's) = 20 mum) of the human FSH-R [14].
• Syntheses and evaluation of antioxidant activity of sydnonyl substituted thiazolidinone and thiazoline derivatives [15].

Analytical, diagnostic and therapeutic context of GW0072

• The compounds VIg-l have two chiral centers in each thiazolidinone moiety so two diastereomers are possible, but on crystallization and repeated chromatography, one diastereomer was obtained [16].

References