Addendum: A cellular chemical probe targeting the chromodomains of Polycomb repressive complex 1

Abstract

In the version of this article originally published, several lines of text in the last paragraph of the right column on page 1 of the PDF were transposed into the bottom paragraph of the left column. The affected text of the left column should read "The ATP-dependent activities of the BAF (SWI/SNF) chromatin remodeling complexes affect the positioning of nucleosomes on DNA and thereby many cellular processes related to chromatin structure, including transcription, DNA repair and decatenation of chromosomes during mitosis 12,13. " The affected text of the right column should read "SMARCA2/4 BD inhibitors are thus precluded from use for the treatment of SMARCA4 mutant cancers but could provide attractive ligands for PROTAC conjugation. Small molecules binding to other bromodomains have been successfully converted into PROTACs by conjugating them with structures capable of binding to the E3 ligases von Hippel−Lindau (VHL) or cereblon 5,6,10,11,25,26,27. " The errors have been corrected in the PDF version of the paper.

Reprogramming CBX8-PRC1 function with a positive allosteric modulator

“…The availability of a negative control is important to enable cellular and in vivo studies to be carried out with a matched pair of compounds that are as similar as possible in their structure, physical properties, and off-target profiles, while differing greatly in their on-target activity. Based on prior SAR, which showed that epimers at the leucine position did not bind to CBX CDs ( Stuckey et al, 2019 ), we substituted L-cyclobutyl glycine for D-cyclobutyl glycine resulting in compound 35 ( Figure 5A , bottom). As expected, compound 35 displayed a negligible effect on de-repression of GFP in the CBX8 reporter assay ( Figure 5B ).…”

Reprogramming Cbx8-Prc1 Function With a Positive Allosteric Modulator

“…Our search for a negative control for UNC7040 illustrates some of the challenges in creation of the ideal negative control that are perhaps not widely appreciated. Based on prior SAR, that showed that epimers at the leucine position did not bind to CBX CDs (Stuckey et al, 2019), we substituted L-cyclobutyl glycine for D-cyclobutyl glycine resulting in compound 35 ( Figure 5A , bottom). As expected, compound 35 displayed a negligible effect on de-repression of GFP in the CBX8 reporter assay ( Figure 5B ).…”

Prognostic and immunological value of Chromobox family genes in Pan-Cancer

“…The purpose of these molecules is to inhibit the reader function of the CBX protein or to dissociate the PRC1 complex. UNC3866 [30] is a recently reported peptidyl chemical probe for PRC1.It can effectively inhibit the proliferation of PC3 cells by selectively binding to CBX7 [31] . It is recommended that more speci c PRC inhibitors can be developed in the future.…”