PDB 7bch citation summary ‹ Protein Data Bank in Europe (PDBe) ‹ EMBL-EBI

Structural Analysis and Development of Notum Fragment Screening Hits.

Zhao Y, Mahy W, Willis NJ, Woodward HL, Steadman D, Bayle ED, Atkinson BN, Sipthorp J, Vecchia L, Ruza RR, Harlos K, Jeganathan F, Constantinou S, Costa A, Kjær S, Bictash M, Salinas PC, Whiting P, Vincent JP, Fish PV, Jones EY

ACS Chem Neurosci 13 2060-2077 (2022)

Related entries: 7b4x, 7b84, 7b86, 7b87, 7b89, 7b8c, 7b8d, 7b8f, 7b8g, 7b8j, 7b8k, 7b8l, 7b8m, 7b8n, 7b8o, 7b8u, 7b8x, 7b8y, 7b8z, 7b98, 7b99, 7b9d, 7b9i, 7b9n, 7b9u, 7ba1, 7bac, 7bap, 7bc8, 7bc9, 7bcc, 7bcd, 7bcf, 7bci, 7bck, 7bcl, 7bd2, 7bd3, 7bd4, 7bd5, 7bd6, 7bd8, 7bd9, 7bda, 7bdb, 7bdc, 7bdd, 7bdf, 7bdg, 7bdh

Cited: 3 times

PMID: 35731924

10.1021/acschemneuro.2c00325

Abstract

The Wnt signaling suppressor Notum is a promising target for osteoporosis, Alzheimer's disease, and colorectal cancers. To develop novel Notum inhibitors, we used an X-ray crystallographic fragment screen with the Diamond-SGC Poised Library (DSPL) and identified 59 fragment hits from the analysis of 768 data sets. Fifty-eight of the hits were found bound at the enzyme catalytic pocket with potencies ranging from 0.5 to >1000 μM. Analysis of the fragments' diverse binding modes, enzymatic inhibitory activities, and chemical properties led to the selection of six hits for optimization, and five of these resulted in improved Notum inhibitory potencies. One hit, 1

Articles - 7bch mentioned but not cited (1)

Structural Analysis and Development of Notum Fragment Screening Hits. Zhao Y, Mahy W, Willis NJ, Woodward HL, Steadman D, Bayle ED, Atkinson BN, Sipthorp J, Vecchia L, Ruza RR, Harlos K, Jeganathan F, Constantinou S, Costa A, Kjær S, Bictash M, Salinas PC, Whiting P, Vincent JP, Fish PV, Jones EY. ACS Chem Neurosci 13 2060-2077 (2022)

Articles citing this publication (2)

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. J Med Chem 65 7212-7230 (2022)
Notum enhances gastric cancer stem-like cell properties through upregulation of Sox2 by PI3K/AKT signaling pathway. Liu Y, Chen H, Xiao L, Dong P, Ma Y, Zhou Y, Yang J, Bian B, Xie G, Chen L, Shen L. Cell Oncol (Dordr) 47 463-480 (2024)

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