Matches in SemOpenAlex for { <https://semopenalex.org/work/W2980281366> ?p ?o ?g. }
- W2980281366 endingPage "71" @default.
- W2980281366 startingPage "62" @default.
- W2980281366 abstract "The class Frizzled (FZD) or class F of G protein–coupled receptors consists of 10 FZD paralogues and Smoothened (SMO). FZDs coordinate wingless/Int-1 signaling and SMO mediates Hedgehog signaling. Class F receptor signaling is intrinsically important for embryonic development and its dysregulation leads to diseases, including diverse forms of tumors. With regard to the importance of class F signaling in human disease, these receptors provide an attractive target for therapeutics, exemplified by the use of SMO antagonists for the treatment of basal cell carcinoma. Here, we review recent structural insights in combination with a more detailed functional understanding of class F receptor activation, G protein coupling, conformation-based functional selectivity, and mechanistic details of activating cancer mutations, which will lay the basis for further development of class F–targeting small molecules for human therapy. <h3>SIGNIFICANCE STATEMENT</h3> Stimulated by recent insights into the activation mechanisms of class F receptors from structural and functional analysis of Frizzled and Smoothened, we aim to summarize what we know about the molecular details of ligand binding, agonist-driven conformational changes, and class F receptor activation. A better understanding of receptor activation mechanisms will allow us to engage in structure- and mechanism-driven drug discovery with the potential to develop more isoform-selective and potentially pathway-selective drugs for human therapy." @default.
- W2980281366 created "2019-10-18" @default.
- W2980281366 creator A5025877135 @default.
- W2980281366 creator A5060927839 @default.
- W2980281366 creator A5077735277 @default.
- W2980281366 date "2019-10-07" @default.
- W2980281366 modified "2023-10-01" @default.
- W2980281366 title "Molecular Pharmacology of Class F Receptor Activation" @default.
- W2980281366 cites W1539479682 @default.
- W2980281366 cites W1543862028 @default.
- W2980281366 cites W1549826613 @default.
- W2980281366 cites W1833104430 @default.
- W2980281366 cites W1877572006 @default.
- W2980281366 cites W1907833971 @default.
- W2980281366 cites W1918709511 @default.
- W2980281366 cites W1927572613 @default.
- W2980281366 cites W1964129602 @default.
- W2980281366 cites W1970736649 @default.
- W2980281366 cites W1971767775 @default.
- W2980281366 cites W1974094726 @default.
- W2980281366 cites W1974319293 @default.
- W2980281366 cites W1977462853 @default.
- W2980281366 cites W1994620081 @default.
- W2980281366 cites W1996473157 @default.
- W2980281366 cites W1997697061 @default.
- W2980281366 cites W1998796212 @default.
- W2980281366 cites W1998845518 @default.
- W2980281366 cites W2002953019 @default.
- W2980281366 cites W2006419043 @default.
- W2980281366 cites W2008956402 @default.
- W2980281366 cites W2015296123 @default.
- W2980281366 cites W2021193175 @default.
- W2980281366 cites W2023040415 @default.
- W2980281366 cites W2025453970 @default.
- W2980281366 cites W2029824690 @default.
- W2980281366 cites W2031522329 @default.
- W2980281366 cites W2032117493 @default.
- W2980281366 cites W2035809306 @default.
- W2980281366 cites W2036465329 @default.
- W2980281366 cites W2036833206 @default.
- W2980281366 cites W2041211150 @default.
- W2980281366 cites W2047224295 @default.
- W2980281366 cites W2050839067 @default.
- W2980281366 cites W2053387793 @default.
- W2980281366 cites W2053996795 @default.
- W2980281366 cites W2059857664 @default.
- W2980281366 cites W2060874643 @default.
- W2980281366 cites W2063112284 @default.
- W2980281366 cites W2064153835 @default.
- W2980281366 cites W2065431388 @default.
- W2980281366 cites W2065914048 @default.
- W2980281366 cites W2067474367 @default.
- W2980281366 cites W2067937471 @default.
- W2980281366 cites W2070524647 @default.
- W2980281366 cites W2072008436 @default.
- W2980281366 cites W2077282333 @default.
- W2980281366 cites W2079796219 @default.
- W2980281366 cites W2085775776 @default.
- W2980281366 cites W2087500600 @default.
- W2980281366 cites W2088942336 @default.
- W2980281366 cites W2090455515 @default.
- W2980281366 cites W2092235051 @default.
- W2980281366 cites W2097394603 @default.
- W2980281366 cites W2108233365 @default.
- W2980281366 cites W2108707301 @default.
- W2980281366 cites W2108981830 @default.
- W2980281366 cites W2109254532 @default.
- W2980281366 cites W2111826622 @default.
- W2980281366 cites W2114355635 @default.
- W2980281366 cites W2114984846 @default.
- W2980281366 cites W2121621910 @default.
- W2980281366 cites W2128801071 @default.
- W2980281366 cites W2131631752 @default.
- W2980281366 cites W2132682425 @default.
- W2980281366 cites W2134597651 @default.
- W2980281366 cites W2135102992 @default.
- W2980281366 cites W2136521447 @default.
- W2980281366 cites W2139129258 @default.
- W2980281366 cites W2140154776 @default.
- W2980281366 cites W2144558833 @default.
- W2980281366 cites W2145845789 @default.
- W2980281366 cites W2147864074 @default.
- W2980281366 cites W2152653728 @default.
- W2980281366 cites W2159374159 @default.
- W2980281366 cites W2159970646 @default.
- W2980281366 cites W2163171072 @default.
- W2980281366 cites W2164310262 @default.
- W2980281366 cites W2167857702 @default.
- W2980281366 cites W2170898400 @default.
- W2980281366 cites W2171756360 @default.
- W2980281366 cites W2172553467 @default.
- W2980281366 cites W2172595079 @default.
- W2980281366 cites W2189059614 @default.
- W2980281366 cites W2239090104 @default.
- W2980281366 cites W2258467325 @default.
- W2980281366 cites W2268692103 @default.
- W2980281366 cites W2282259832 @default.
- W2980281366 cites W2294157538 @default.