3',4'-Bis-difluoromethoxycinnamoylanthranilate (FT061): An orally-active antifibrotic agent that reduces albuminuria in a rat model of progressive diabetic nephropathy

Spencer John Williams, Steven C Zammit, Alison J Cox, David Shackleford, Julia Morizzi, Yuan Zhang, Andrew Keith Powell, Richard E Gilbert, Henry Krum, Darren James Kelly

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Cinnamoylanthranilates including tranilast have been identified as promising antifibrotics that can reduce fibrosis occurring in the kidney during diabetes, thereby delaying and/or preventing kidney dysfunction. Structure-activity relationships aimed at improving potency and metabolic stability have led to the discovery of FT061. This compound, which bears a bis-difluoromethoxy catechol, attenuates TGF-beta-stimulated production of collagen in cultured renal mesangial cells (approx 50 at 3 mu M). When dosed orally at 20 mg/kg to male Sprague Dawley rats, FT061 exhibited a high bioavailability (73 ), C-max of 200 mu M and T-max of 150 min, and a half-life of 5.4 h. FT061 reduced albuminuria when orally dosed in rats at 200 mg kg/day in a late intervention study of a rat model of progressive diabetic nephropathy.
Original languageEnglish
Pages (from-to)6868 - 6873
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number24
DOIs
Publication statusPublished - 2013

Cite this

Williams, Spencer John ; Zammit, Steven C ; Cox, Alison J ; Shackleford, David ; Morizzi, Julia ; Zhang, Yuan ; Powell, Andrew Keith ; Gilbert, Richard E ; Krum, Henry ; Kelly, Darren James. / 3',4'-Bis-difluoromethoxycinnamoylanthranilate (FT061): An orally-active antifibrotic agent that reduces albuminuria in a rat model of progressive diabetic nephropathy. In: Bioorganic and Medicinal Chemistry Letters. 2013 ; Vol. 23, No. 24. pp. 6868 - 6873.
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abstract = "Cinnamoylanthranilates including tranilast have been identified as promising antifibrotics that can reduce fibrosis occurring in the kidney during diabetes, thereby delaying and/or preventing kidney dysfunction. Structure-activity relationships aimed at improving potency and metabolic stability have led to the discovery of FT061. This compound, which bears a bis-difluoromethoxy catechol, attenuates TGF-beta-stimulated production of collagen in cultured renal mesangial cells (approx 50 at 3 mu M). When dosed orally at 20 mg/kg to male Sprague Dawley rats, FT061 exhibited a high bioavailability (73 ), C-max of 200 mu M and T-max of 150 min, and a half-life of 5.4 h. FT061 reduced albuminuria when orally dosed in rats at 200 mg kg/day in a late intervention study of a rat model of progressive diabetic nephropathy.",
author = "Williams, {Spencer John} and Zammit, {Steven C} and Cox, {Alison J} and David Shackleford and Julia Morizzi and Yuan Zhang and Powell, {Andrew Keith} and Gilbert, {Richard E} and Henry Krum and Kelly, {Darren James}",
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3',4'-Bis-difluoromethoxycinnamoylanthranilate (FT061): An orally-active antifibrotic agent that reduces albuminuria in a rat model of progressive diabetic nephropathy. / Williams, Spencer John; Zammit, Steven C; Cox, Alison J; Shackleford, David; Morizzi, Julia; Zhang, Yuan; Powell, Andrew Keith; Gilbert, Richard E; Krum, Henry; Kelly, Darren James.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 24, 2013, p. 6868 - 6873.

Research output: Contribution to journalArticleResearchpeer-review

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