452343-18-9Relevant academic research and scientific papers
Formulated and/or co-formulated liposome compositions containing TFGB antagonist prodrugs useful in the treatment of cancer and methods thereof
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Paragraph 0495, (2021/08/27)
Formulated and/or co-formulated liposomes (LNP) and solid-lipid nanoparticles (SLNP) comprising TB Prodrugs and methods of making the LNPs and SLNPs are disclosed herein. The TB prodrug compositions comprise a drug moiety, a lipid moiety, and linkage unit
Discovery of 4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N- (tetrahydro-2H-pyran-4-yl)benzamide (GW788388): A potent, selective, and orally active transforming growth factor-β type I receptor inhibitor
Gellibert, Fran?oise,De Gouville, Anne-Charlotte,Woolven, James,Mathews, Neil,Nguyen, Van-Loc,Bertho-Ruault, Cécile,Patikis, Angela,Grygielko, Eugene T.,Laping, Nicholas J.,Huet, Stéphane
, p. 2210 - 2221 (2007/10/03)
Inhibitors of transforming growth factor β (TGF-β) type I receptor (ALK5) offer a novel approach for the treatment of fibrotic diseases such as renal, hepatic, and pulmonary fibrosis. The optimization of a novel phenylpyridine pyrazole series (1a) led to the identification of potent, selective, and orally active ALK5 inhibitors. The cellular potency and pharmacokinetics profiles of these derivatives were improved and several compounds presented antifibrotic activity when orally administered to rats in an acute liver model of dimethylnitrosamine- (DMN-) induced expression of collagen IA1 mRNA, a major gene contributing to excessive extra cellular matrix deposit. One of the most potent ALK5 inhibitors identified in this chemical series, compound 13d (GW788388), reduced the expression of collagen IA1 by 80% at a dose of 1 mg/kg twice a day (b.i.d.). This compound significantly reduced the expression of collagen IA1 mRNA when administered orally at 10 mg/kg once a day (u.i.d.) in a model of puromycin aminonucleoside-induced renal fibrosis.
