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- W4220933807 abstract "With innumerable clinical failures of target-specific drug candidates for multifactorial diseases, such as Alzheimer’s disease (AD), which remains inefficiently treated, the advent of multitarget drug discovery has brought a new breath of hope. Here, we disclose a class of 6-chlorotacrine (huprine)–TPPU hybrids as dual inhibitors of the enzymes soluble epoxide hydrolase (sEH) and acetylcholinesterase (AChE), a multitarget profile to provide cumulative effects against neuroinflammation and memory impairment. Computational studies confirmed the gorge-wide occupancy of both enzymes, from the main site to a secondary site, including a so far non-described AChE cryptic pocket. The lead compound displayed in vitro dual nanomolar potencies, adequate brain permeability, aqueous solubility, human microsomal stability, lack of neurotoxicity, and it rescued memory, synaptic plasticity, and neuroinflammation in an AD mouse model, after low dose chronic oral administration." @default.
- W4220933807 created "2022-04-03" @default.
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- W4220933807 date "2022-03-10" @default.
- W4220933807 modified "2023-10-17" @default.
- W4220933807 title "Discovery and In Vivo Proof of Concept of a Highly Potent Dual Inhibitor of Soluble Epoxide Hydrolase and Acetylcholinesterase for the Treatment of Alzheimer’s Disease" @default.
- W4220933807 cites W1971048984 @default.
- W4220933807 cites W1972719099 @default.
- W4220933807 cites W1981775239 @default.
- W4220933807 cites W1993672505 @default.
- W4220933807 cites W1993961204 @default.
- W4220933807 cites W2004822259 @default.
- W4220933807 cites W2009221410 @default.
- W4220933807 cites W2012076046 @default.
- W4220933807 cites W2025223727 @default.
- W4220933807 cites W2026976753 @default.
- W4220933807 cites W2029954340 @default.
- W4220933807 cites W2037535298 @default.
- W4220933807 cites W2039781258 @default.
- W4220933807 cites W2044444984 @default.
- W4220933807 cites W2060079863 @default.
- W4220933807 cites W2064391088 @default.
- W4220933807 cites W2072683434 @default.
- W4220933807 cites W2074593965 @default.
- W4220933807 cites W2074722271 @default.
- W4220933807 cites W2089815158 @default.
- W4220933807 cites W2092538255 @default.
- W4220933807 cites W2096657589 @default.
- W4220933807 cites W2100561975 @default.
- W4220933807 cites W2102479939 @default.
- W4220933807 cites W2106140689 @default.
- W4220933807 cites W2117356638 @default.
- W4220933807 cites W2121802937 @default.
- W4220933807 cites W2128276019 @default.
- W4220933807 cites W2128671521 @default.
- W4220933807 cites W2129077714 @default.
- W4220933807 cites W2130479394 @default.
- W4220933807 cites W2135732933 @default.
- W4220933807 cites W2142178921 @default.
- W4220933807 cites W2147993766 @default.
- W4220933807 cites W2149196013 @default.
- W4220933807 cites W2152147380 @default.
- W4220933807 cites W2156012433 @default.
- W4220933807 cites W2158984087 @default.
- W4220933807 cites W2313116527 @default.
- W4220933807 cites W2315120195 @default.
- W4220933807 cites W2327787157 @default.
- W4220933807 cites W2330799739 @default.
- W4220933807 cites W2332712348 @default.
- W4220933807 cites W2339299551 @default.
- W4220933807 cites W2404280981 @default.
- W4220933807 cites W2554932040 @default.
- W4220933807 cites W2572208524 @default.
- W4220933807 cites W2750477650 @default.
- W4220933807 cites W2765584833 @default.
- W4220933807 cites W2777580612 @default.
- W4220933807 cites W2789955563 @default.
- W4220933807 cites W2884740260 @default.
- W4220933807 cites W2886819196 @default.
- W4220933807 cites W2890186102 @default.
- W4220933807 cites W2906335005 @default.
- W4220933807 cites W2952159156 @default.
- W4220933807 cites W2954500169 @default.
- W4220933807 cites W2957558461 @default.
- W4220933807 cites W3010998607 @default.
- W4220933807 cites W3021284300 @default.
- W4220933807 cites W3029284941 @default.
- W4220933807 cites W3043986491 @default.
- W4220933807 cites W3045058053 @default.
- W4220933807 cites W3083862941 @default.
- W4220933807 cites W3088113304 @default.
- W4220933807 cites W3091160298 @default.
- W4220933807 cites W3092032238 @default.
- W4220933807 cites W3094344690 @default.
- W4220933807 cites W3106851243 @default.
- W4220933807 cites W3112030344 @default.
- W4220933807 cites W3113520298 @default.
- W4220933807 cites W3113989042 @default.