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Design of a Potent, Selective, and Brain-Penetrant Inhibitor of Wnt-Deactivating Enzyme Notum by Optimization of a Crystallographic Fragment Hit.
Willis NJ, Mahy W, Sipthorp J, Zhao Y, Woodward HL, Atkinson BN, Bayle ED, Svensson F, Frew S, Jeganathan F, Monaghan A, Benvegnù S, Jolly S, Vecchia L, Ruza RR, Kjær S, Howell S, Snijders AP, Bictash M, Salinas PC, Vincent JP, Jones EY, Whiting P, Fish PV. Willis NJ, et al. Among authors: jones ey. J Med Chem. 2022 May 26;65(10):7212-7230. doi: 10.1021/acs.jmedchem.2c00162. Epub 2022 May 10. J Med Chem. 2022. PMID: 35536179 Free PMC article.
Notum deacylates Wnt proteins to suppress signalling activity.
Kakugawa S, Langton PF, Zebisch M, Howell S, Chang TH, Liu Y, Feizi T, Bineva G, O'Reilly N, Snijders AP, Jones EY, Vincent JP. Kakugawa S, et al. Among authors: jones ey. Nature. 2015 Mar 12;519(7542):187-192. doi: 10.1038/nature14259. Epub 2015 Feb 25. Nature. 2015. PMID: 25731175 Free PMC article.
Scaffold-hopping identifies furano[2,3-d]pyrimidine amides as potent Notum inhibitors.
Atkinson BN, Steadman D, Mahy W, Zhao Y, Sipthorp J, Bayle ED, Svensson F, Papageorgiou G, Jeganathan F, Frew S, Monaghan A, Bictash M, Jones EY, Fish PV. Atkinson BN, et al. Among authors: jones ey. Bioorg Med Chem Lett. 2020 Feb 1;30(3):126751. doi: 10.1016/j.bmcl.2019.126751. Epub 2019 Oct 28. Bioorg Med Chem Lett. 2020. PMID: 31862412 Free PMC article.
288 results