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- W2884518403 abstract "Oxidative stress is an underlying component of acute and chronic kidney disease. Apoptosis signal-regulating kinase 1 (ASK1) is a widely expressed redox-sensitive serine threonine kinase that activates p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase kinases, and induces apoptotic, inflammatory, and fibrotic signaling in settings of oxidative stress. We describe the discovery and characterization of a potent and selective small-molecule inhibitor of ASK1, GS-444217, and demonstrate the therapeutic potential of ASK1 inhibition to reduce kidney injury and fibrosis. Activation of the ASK1 pathway in glomerular and tubular compartments was confirmed in renal biopsies from patients with diabetic kidney disease (DKD) and was decreased by GS-444217 in several rodent models of kidney injury and fibrosis that collectively represented the hallmarks of DKD pathology. Treatment with GS-444217 reduced progressive inflammation and fibrosis in the kidney and halted glomerular filtration rate decline. Combination of GS-444217 with enalapril, an angiotensin-converting enzyme inhibitor, led to a greater reduction in proteinuria and regression of glomerulosclerosis. These results identify ASK1 as an important target for renal disease and support the clinical development of an ASK1 inhibitor for the treatment of DKD." @default.
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- W2884518403 date "2018-07-19" @default.
- W2884518403 modified "2023-10-14" @default.
- W2884518403 title "ASK1 contributes to fibrosis and dysfunction in models of kidney disease" @default.
- W2884518403 cites W1558823847 @default.
- W2884518403 cites W1595278394 @default.
- W2884518403 cites W1699432502 @default.
- W2884518403 cites W1861665996 @default.
- W2884518403 cites W1864228662 @default.
- W2884518403 cites W1892795191 @default.
- W2884518403 cites W1967447462 @default.
- W2884518403 cites W1968104064 @default.
- W2884518403 cites W1969268163 @default.
- W2884518403 cites W1970532577 @default.
- W2884518403 cites W1973707785 @default.
- W2884518403 cites W1973850434 @default.
- W2884518403 cites W1981852031 @default.
- W2884518403 cites W1986751708 @default.
- W2884518403 cites W1987979328 @default.
- W2884518403 cites W1988212011 @default.
- W2884518403 cites W1991405963 @default.
- W2884518403 cites W1998174161 @default.
- W2884518403 cites W2003934140 @default.
- W2884518403 cites W2005188572 @default.
- W2884518403 cites W2011409573 @default.
- W2884518403 cites W2030555517 @default.
- W2884518403 cites W2033431458 @default.
- W2884518403 cites W2034580062 @default.
- W2884518403 cites W2035581994 @default.
- W2884518403 cites W2039799010 @default.
- W2884518403 cites W2042601256 @default.
- W2884518403 cites W2043873569 @default.
- W2884518403 cites W2044147293 @default.
- W2884518403 cites W2047402931 @default.
- W2884518403 cites W2050522050 @default.
- W2884518403 cites W2054992864 @default.
- W2884518403 cites W2066471150 @default.
- W2884518403 cites W2072981794 @default.
- W2884518403 cites W2075089162 @default.
- W2884518403 cites W2078317541 @default.
- W2884518403 cites W2079654264 @default.
- W2884518403 cites W2080509111 @default.
- W2884518403 cites W2082967236 @default.
- W2884518403 cites W2089934320 @default.
- W2884518403 cites W2092389955 @default.
- W2884518403 cites W2100772783 @default.
- W2884518403 cites W2102235083 @default.
- W2884518403 cites W2104167564 @default.
- W2884518403 cites W2107238909 @default.
- W2884518403 cites W2107751591 @default.
- W2884518403 cites W2116938728 @default.
- W2884518403 cites W2123206756 @default.
- W2884518403 cites W2123989622 @default.
- W2884518403 cites W2125013655 @default.
- W2884518403 cites W2127336805 @default.
- W2884518403 cites W2127513926 @default.
- W2884518403 cites W2131349854 @default.
- W2884518403 cites W2131410256 @default.
- W2884518403 cites W2136490577 @default.
- W2884518403 cites W2139947959 @default.
- W2884518403 cites W2141528038 @default.
- W2884518403 cites W2142986295 @default.
- W2884518403 cites W2159574886 @default.
- W2884518403 cites W2160934553 @default.
- W2884518403 cites W2161197757 @default.
- W2884518403 cites W2164794447 @default.
- W2884518403 cites W2165160652 @default.
- W2884518403 cites W2165262170 @default.
- W2884518403 cites W2170783508 @default.
- W2884518403 cites W2188526593 @default.
- W2884518403 cites W2192080449 @default.
- W2884518403 cites W2289487108 @default.