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- W4252363154 abstract "The mechanism-based risk for hyperkalemia has limited the use of mineralocorticoid receptor antagonists (MRAs) like eplerenone in cardio-renal diseases. Here, we describe the structure and property-driven lead generation and optimization, which resulted in identification of MR modulators ( S)-1 and ( S)-33. Both compounds were partial MRAs but still demonstrated equally efficacious organ protection as eplerenone after 4 weeks of treatment in uni-nephrectomized rats on high-salt diet and aldosterone infusion. Importantly, and in sharp contrast to eplerenone, this was achieved without substantial changes to the urine Na+/K+ ratio after acute treatment in rat, which predicts a reduced risk for hyperkalemia. This work led to selection of ( S)-1 (AZD9977) as the clinical candidate for treating MR-mediated cardio-renal diseases, including chronic kidney disease and heart failure. On the basis of our findings, we propose an empirical model for prediction of compounds with low risk of affecting the urinary Na+/K+ ratio in vivo." @default.
- W4252363154 created "2022-05-12" @default.
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- W4252363154 date "2018-12-31" @default.
- W4252363154 modified "2023-10-13" @default.
- W4252363154 title "Identification of Mineralocorticoid Receptor Modulators with Low Impact on Electrolyte Homeostasis but Maintained Organ Protection" @default.
- W4252363154 cites W1485915558 @default.
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- W4252363154 cites W1975455257 @default.
- W4252363154 cites W1977122152 @default.
- W4252363154 cites W2005531594 @default.
- W4252363154 cites W2007841265 @default.
- W4252363154 cites W2010799694 @default.
- W4252363154 cites W2013817923 @default.
- W4252363154 cites W2015064559 @default.
- W4252363154 cites W2017315940 @default.
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- W4252363154 cites W2020811647 @default.
- W4252363154 cites W2052181661 @default.
- W4252363154 cites W2052724934 @default.
- W4252363154 cites W2056455169 @default.
- W4252363154 cites W2058515290 @default.
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- W4252363154 cites W2079169053 @default.
- W4252363154 cites W2083662856 @default.
- W4252363154 cites W2086458312 @default.
- W4252363154 cites W2086803509 @default.
- W4252363154 cites W2092312413 @default.
- W4252363154 cites W2104209472 @default.
- W4252363154 cites W2111945961 @default.
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- W4252363154 cites W2116389513 @default.
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- W4252363154 cites W2124087925 @default.
- W4252363154 cites W2131059659 @default.
- W4252363154 cites W2131290017 @default.
- W4252363154 cites W2141543068 @default.
- W4252363154 cites W2147273166 @default.
- W4252363154 cites W2147621031 @default.
- W4252363154 cites W2152072062 @default.
- W4252363154 cites W2157547579 @default.
- W4252363154 cites W2166200293 @default.
- W4252363154 cites W2166459244 @default.
- W4252363154 cites W2171678503 @default.
- W4252363154 cites W2174790057 @default.
- W4252363154 cites W2209117202 @default.
- W4252363154 cites W2227911728 @default.
- W4252363154 cites W2261847207 @default.
- W4252363154 cites W2316149257 @default.
- W4252363154 cites W2331016119 @default.
- W4252363154 cites W2372575515 @default.
- W4252363154 cites W2410506030 @default.
- W4252363154 cites W2510521632 @default.
- W4252363154 cites W2559744632 @default.
- W4252363154 cites W2569639894 @default.
- W4252363154 cites W2588812754 @default.
- W4252363154 cites W2769696378 @default.
- W4252363154 cites W2782048540 @default.
- W4252363154 cites W2792578296 @default.
- W4252363154 cites W2951085180 @default.
- W4252363154 cites W2953102654 @default.